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Gene Information

Gene symbol: CEACAM5

Gene name: carcinoembryonic antigen-related cell adhesion molecule 5

HGNC ID: 1817

Synonyms: CD66e

Related Genes

# Gene Symbol Number of hits
1 AD5 1 hits
2 AFP 1 hits
3 ALB 1 hits
4 ANKRD36B 1 hits
5 APC 1 hits
6 ATP2C1 1 hits
7 BIRC5 1 hits
8 CAP1 1 hits
9 CCL11 1 hits
10 CCNB1 1 hits
11 CD4 1 hits
12 CD40 1 hits
13 CD40LG 1 hits
14 CD46 1 hits
15 CD58 1 hits
16 CD63 1 hits
17 CD79A 1 hits
18 CD83 1 hits
19 CD86 1 hits
20 CD8A 1 hits
21 CEACAM1 1 hits
22 CSF1 1 hits
23 CSF2 1 hits
24 CSF3 1 hits
25 CTLA4 1 hits
26 CXCL10 1 hits
27 CXCL14 1 hits
28 EGFR 1 hits
29 ERBB2 1 hits
30 FAS 1 hits
31 FOLH1 1 hits
32 HBB 1 hits
33 HLA-A 1 hits
34 HSPA14 1 hits
35 ICAM1 1 hits
36 IFNA1 1 hits
37 IFNG 1 hits
38 IGKV2-23 1 hits
39 IL10 1 hits
40 IL12A 1 hits
41 IL18 1 hits
42 IL1B 1 hits
43 IL2 1 hits
44 IL2RA 1 hits
45 IL4 1 hits
46 IL5 1 hits
47 IL6 1 hits
48 IL8 1 hits
49 KLK3 1 hits
50 MAGEA1 1 hits
51 MAGEA2 1 hits
52 MAGEA3 1 hits
53 MBP 1 hits
54 MLANA 1 hits
55 MMP8 1 hits
56 MSLN 1 hits
57 MUC1 1 hits
58 MUC16 1 hits
59 PLAG1 1 hits
60 PTGS2 1 hits
61 S100A1 1 hits
62 SLC5A5 1 hits
63 TACSTD1 1 hits
64 TBX1 1 hits
65 TERT 1 hits
66 TH1L 1 hits
67 TIMP1 1 hits
68 TLR7 1 hits
69 TLR9 1 hits
70 TNF 1 hits
71 TNFRSF9 1 hits
72 TP53 1 hits
73 TRAF3 1 hits
74 VEGFC 1 hits
75 WT1 1 hits

Related Sentences

# PMID Sentence
1 1557930 The effect of liposome encapsulation on the antibody response to bovine serum albumin (BSA), human carcinoembryonic antigen (CEA) and sheep IgG (sIgG) has been determined in the mouse.
2 7882341 We have constructed mRNA transcripts encoding luciferase and human carcinoembryonic antigen (CEA) which are capped, polyadenylated, and stabilized by human beta-globin 5' and 3' untranslated regions.
3 8118800 Lymphocytes from 2 of 5 mice had interleukin 2/interleukin 4 release in response to CEA.
4 8625312 In this report, data indicate that IL-2 administration can appreciably augment the therapeutic effect of a single immunization of a recombinant vaccinia virus-carcinoembryonic antigen (rV-CEA) vaccine using a CEA-expressing syngeneic experimental murine model system.
5 8625312 Moreover, the combination of rV-CEA and IL-2 induces systemic immunity, which protects those tumor-free mice from subsequent rechallenge with the CEA-expressing tumor cells.
6 8625312 Cellular immune assays revealed that the addition of IL-2 to rV-CEA immunization significantly increased the CEA-specific T-cell proliferative responses as well as the cytolytic T-cell responses when compared with rV-CEA immunization alone.
7 8625312 The enhanced CEA-specific immune response, coupled with the improved experimental therapeutic outcome following IL-2 administration, suggests that treatment with that cytokine may effectively substitute for multiple rV-CEA immunizations in active-specific immunotherapy clinical protocols directed at CEA-expressing tumors.
8 8625312 In this report, data indicate that IL-2 administration can appreciably augment the therapeutic effect of a single immunization of a recombinant vaccinia virus-carcinoembryonic antigen (rV-CEA) vaccine using a CEA-expressing syngeneic experimental murine model system.
9 8625312 Moreover, the combination of rV-CEA and IL-2 induces systemic immunity, which protects those tumor-free mice from subsequent rechallenge with the CEA-expressing tumor cells.
10 8625312 Cellular immune assays revealed that the addition of IL-2 to rV-CEA immunization significantly increased the CEA-specific T-cell proliferative responses as well as the cytolytic T-cell responses when compared with rV-CEA immunization alone.
11 8625312 The enhanced CEA-specific immune response, coupled with the improved experimental therapeutic outcome following IL-2 administration, suggests that treatment with that cytokine may effectively substitute for multiple rV-CEA immunizations in active-specific immunotherapy clinical protocols directed at CEA-expressing tumors.
12 8625312 In this report, data indicate that IL-2 administration can appreciably augment the therapeutic effect of a single immunization of a recombinant vaccinia virus-carcinoembryonic antigen (rV-CEA) vaccine using a CEA-expressing syngeneic experimental murine model system.
13 8625312 Moreover, the combination of rV-CEA and IL-2 induces systemic immunity, which protects those tumor-free mice from subsequent rechallenge with the CEA-expressing tumor cells.
14 8625312 Cellular immune assays revealed that the addition of IL-2 to rV-CEA immunization significantly increased the CEA-specific T-cell proliferative responses as well as the cytolytic T-cell responses when compared with rV-CEA immunization alone.
15 8625312 The enhanced CEA-specific immune response, coupled with the improved experimental therapeutic outcome following IL-2 administration, suggests that treatment with that cytokine may effectively substitute for multiple rV-CEA immunizations in active-specific immunotherapy clinical protocols directed at CEA-expressing tumors.
16 8625312 In this report, data indicate that IL-2 administration can appreciably augment the therapeutic effect of a single immunization of a recombinant vaccinia virus-carcinoembryonic antigen (rV-CEA) vaccine using a CEA-expressing syngeneic experimental murine model system.
17 8625312 Moreover, the combination of rV-CEA and IL-2 induces systemic immunity, which protects those tumor-free mice from subsequent rechallenge with the CEA-expressing tumor cells.
18 8625312 Cellular immune assays revealed that the addition of IL-2 to rV-CEA immunization significantly increased the CEA-specific T-cell proliferative responses as well as the cytolytic T-cell responses when compared with rV-CEA immunization alone.
19 8625312 The enhanced CEA-specific immune response, coupled with the improved experimental therapeutic outcome following IL-2 administration, suggests that treatment with that cytokine may effectively substitute for multiple rV-CEA immunizations in active-specific immunotherapy clinical protocols directed at CEA-expressing tumors.
20 8825120 The T-cell lines were shown to be CD8+ and/or CD4+/CD8+, to lyse EBV transformed B-cells transduced with the CEA gene, and to lyse CEA positive carcinoma cells in a HLA restricted manner.
21 9377571 Single amino acid substitutions were introduced to the CAP1 peptide (YLSGANLNL), an immunogenic HLA-A2+-binding peptide derived from human carcinoembryonic antigen (CEA).
22 9377571 Whereas CAP1 failed to generate CTLs from normal peripheral blood mononuclear cells, the agonist peptide was able to generate CD8+ CTL lines that recognized both the agonist and the native CAP1 sequence.
23 9815645 We report here the serial phenotypic characterization of a CTL line directed against an immunodominant epitope (YLSGANLNL, designated CAP-1) of human carcinoembryonic antigen (CEA).
24 9815645 This CTL line was derived from peripheral blood mononuclear cells of a patient with metastatic carcinoma who had been treated with a recombinant CEA-vaccinia vaccine in a Phase I trial; the CTLs were analyzed through 20 in vitro cycle passages of stimulation with CAP-1 peptide and interleukin 2 in the presence of autologous antigen-presenting cells.
25 9815645 The CTL line was shown to be phenotypically stable in terms of high levels of cytokine (IFN-gamma, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor) production, expression of homing-adhesion molecules, ability to lyse peptide-pulsed targets, and ability to lyse human carcinoma cells endogenously expressing CEA in a MHC-restricted manner.
26 9815645 We report here the serial phenotypic characterization of a CTL line directed against an immunodominant epitope (YLSGANLNL, designated CAP-1) of human carcinoembryonic antigen (CEA).
27 9815645 This CTL line was derived from peripheral blood mononuclear cells of a patient with metastatic carcinoma who had been treated with a recombinant CEA-vaccinia vaccine in a Phase I trial; the CTLs were analyzed through 20 in vitro cycle passages of stimulation with CAP-1 peptide and interleukin 2 in the presence of autologous antigen-presenting cells.
28 9815645 The CTL line was shown to be phenotypically stable in terms of high levels of cytokine (IFN-gamma, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor) production, expression of homing-adhesion molecules, ability to lyse peptide-pulsed targets, and ability to lyse human carcinoma cells endogenously expressing CEA in a MHC-restricted manner.
29 9815645 We report here the serial phenotypic characterization of a CTL line directed against an immunodominant epitope (YLSGANLNL, designated CAP-1) of human carcinoembryonic antigen (CEA).
30 9815645 This CTL line was derived from peripheral blood mononuclear cells of a patient with metastatic carcinoma who had been treated with a recombinant CEA-vaccinia vaccine in a Phase I trial; the CTLs were analyzed through 20 in vitro cycle passages of stimulation with CAP-1 peptide and interleukin 2 in the presence of autologous antigen-presenting cells.
31 9815645 The CTL line was shown to be phenotypically stable in terms of high levels of cytokine (IFN-gamma, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor) production, expression of homing-adhesion molecules, ability to lyse peptide-pulsed targets, and ability to lyse human carcinoma cells endogenously expressing CEA in a MHC-restricted manner.
32 9829759 However, delayed type hypersensitivity to CEA and CEA-specific interleukin-2 release were observed only in the i.m. group, suggesting a qualitative difference in the character of the immune response elicited by the two techniques of DNA immunization.
33 9829838 Eighteen colorectal carcinoma patients without macroscopic disease after surgery were immunized using recombinant (r) human (h) carcinoembryonic antigen (CEA) with (n=9) or without (n=9) the addition of soluble granulocyte/macrophage-colony-stimulating factor (GM-CSF).
34 9829838 All patients (9/9) in the GM-CSF group developed a strong rhCEA-specific proliferative T cell response as well as type I T cells (interferon gamma secretion).
35 9829838 A specific cellular response (proliferation and/or cytokine secretion) against native hCEA could be found in 8/9 patients in the GM-CSF group, although at a significantly lower level than against rhCEA.
36 9829838 Local pharmacological administration of GM-CSF seemed to be a prerequisite for the induction of a strong immunity against baculovirus-produced hCEA protein.
37 9829838 Eighteen colorectal carcinoma patients without macroscopic disease after surgery were immunized using recombinant (r) human (h) carcinoembryonic antigen (CEA) with (n=9) or without (n=9) the addition of soluble granulocyte/macrophage-colony-stimulating factor (GM-CSF).
38 9829838 All patients (9/9) in the GM-CSF group developed a strong rhCEA-specific proliferative T cell response as well as type I T cells (interferon gamma secretion).
39 9829838 A specific cellular response (proliferation and/or cytokine secretion) against native hCEA could be found in 8/9 patients in the GM-CSF group, although at a significantly lower level than against rhCEA.
40 9829838 Local pharmacological administration of GM-CSF seemed to be a prerequisite for the induction of a strong immunity against baculovirus-produced hCEA protein.
41 9829838 Eighteen colorectal carcinoma patients without macroscopic disease after surgery were immunized using recombinant (r) human (h) carcinoembryonic antigen (CEA) with (n=9) or without (n=9) the addition of soluble granulocyte/macrophage-colony-stimulating factor (GM-CSF).
42 9829838 All patients (9/9) in the GM-CSF group developed a strong rhCEA-specific proliferative T cell response as well as type I T cells (interferon gamma secretion).
43 9829838 A specific cellular response (proliferation and/or cytokine secretion) against native hCEA could be found in 8/9 patients in the GM-CSF group, although at a significantly lower level than against rhCEA.
44 9829838 Local pharmacological administration of GM-CSF seemed to be a prerequisite for the induction of a strong immunity against baculovirus-produced hCEA protein.
45 9973217 These mice also developed T(H)1-type CEA-specific CD4+ responses and CEA peptide-specific cytotoxicity.
46 10230872 LI is characterized by CD4+ and CD8+ tumor infiltrating lymphocytes reflecting latent cell-mediated immunity (CMI).
47 10230872 CMI and humoral immune reactivity have been demonstrated to autologous tumor and a variety of tumor-associated antigens (TAA) have been implicated including CEA, HER-2/neu, MAGE-1, p53, T/Tn and MUC-1.
48 10230872 Animal models have employed drug therapy, cytokine transfection, vaccines with autologous tumor, cytokines like interferon alpha (IFN-alpha) and interleukin-2 (IL-2), TAA tumor vaccines, and immunotoxins with evidence of tumor regression by immunologic means.
49 10230872 Positive results have been obtained with natural IFN and interleukins, particularly in combination strategies (but not with high dose recombinant IFN or IL-2), with autologous tumor vaccine (but not yet with transfected autologous tumor); with a mucin carbohydrate vaccine (Theratope) in a combination strategy (but not with mucin core antigen) and with several immunotoxins.
50 10499601 No evidence of CEA-specific lymphoproliferation, interleukin 2 release, delayed-type hypersensitivity, or antibody response was observed.
51 10757021 Coinjection of the CEA vector with a vector encoding either interferon-gamma (IFN gamma) or IL-12 promoted IgG2a isotype anti-CEA antibody production, anti-CEA/P815 CTL activity and greater resistance to CEA/P815 tumor challenge.
52 10757021 As well, CEA/P815-stimulated IFN gamma secretion in vitro was increased, but IL-4 diminished, consistent with a T-helper type 1 (Th1) response.
53 10757021 In contrast, coinjection of the CEA vector with an IL-4 vector increased IgG1 production, but reduced CTL activity and resistance to tumor challenge.
54 10757021 The latter treatment inhibited CEA/P815-dependent IFN gamma production but enhanced IL-4 secretion, consistent with a Th type 2 (Th2) response.
55 10757021 Antitumor immunity was enhanced when the CEA and IL-12 plasmids were coinjected at the same muscle site, but not at separate sites despite increased serum IL-12 levels.
56 10757021 Coinjection of the CEA vector with a vector encoding either interferon-gamma (IFN gamma) or IL-12 promoted IgG2a isotype anti-CEA antibody production, anti-CEA/P815 CTL activity and greater resistance to CEA/P815 tumor challenge.
57 10757021 As well, CEA/P815-stimulated IFN gamma secretion in vitro was increased, but IL-4 diminished, consistent with a T-helper type 1 (Th1) response.
58 10757021 In contrast, coinjection of the CEA vector with an IL-4 vector increased IgG1 production, but reduced CTL activity and resistance to tumor challenge.
59 10757021 The latter treatment inhibited CEA/P815-dependent IFN gamma production but enhanced IL-4 secretion, consistent with a Th type 2 (Th2) response.
60 10757021 Antitumor immunity was enhanced when the CEA and IL-12 plasmids were coinjected at the same muscle site, but not at separate sites despite increased serum IL-12 levels.
61 10757021 Coinjection of the CEA vector with a vector encoding either interferon-gamma (IFN gamma) or IL-12 promoted IgG2a isotype anti-CEA antibody production, anti-CEA/P815 CTL activity and greater resistance to CEA/P815 tumor challenge.
62 10757021 As well, CEA/P815-stimulated IFN gamma secretion in vitro was increased, but IL-4 diminished, consistent with a T-helper type 1 (Th1) response.
63 10757021 In contrast, coinjection of the CEA vector with an IL-4 vector increased IgG1 production, but reduced CTL activity and resistance to tumor challenge.
64 10757021 The latter treatment inhibited CEA/P815-dependent IFN gamma production but enhanced IL-4 secretion, consistent with a Th type 2 (Th2) response.
65 10757021 Antitumor immunity was enhanced when the CEA and IL-12 plasmids were coinjected at the same muscle site, but not at separate sites despite increased serum IL-12 levels.
66 10757021 Coinjection of the CEA vector with a vector encoding either interferon-gamma (IFN gamma) or IL-12 promoted IgG2a isotype anti-CEA antibody production, anti-CEA/P815 CTL activity and greater resistance to CEA/P815 tumor challenge.
67 10757021 As well, CEA/P815-stimulated IFN gamma secretion in vitro was increased, but IL-4 diminished, consistent with a T-helper type 1 (Th1) response.
68 10757021 In contrast, coinjection of the CEA vector with an IL-4 vector increased IgG1 production, but reduced CTL activity and resistance to tumor challenge.
69 10757021 The latter treatment inhibited CEA/P815-dependent IFN gamma production but enhanced IL-4 secretion, consistent with a Th type 2 (Th2) response.
70 10757021 Antitumor immunity was enhanced when the CEA and IL-12 plasmids were coinjected at the same muscle site, but not at separate sites despite increased serum IL-12 levels.
71 10757021 Coinjection of the CEA vector with a vector encoding either interferon-gamma (IFN gamma) or IL-12 promoted IgG2a isotype anti-CEA antibody production, anti-CEA/P815 CTL activity and greater resistance to CEA/P815 tumor challenge.
72 10757021 As well, CEA/P815-stimulated IFN gamma secretion in vitro was increased, but IL-4 diminished, consistent with a T-helper type 1 (Th1) response.
73 10757021 In contrast, coinjection of the CEA vector with an IL-4 vector increased IgG1 production, but reduced CTL activity and resistance to tumor challenge.
74 10757021 The latter treatment inhibited CEA/P815-dependent IFN gamma production but enhanced IL-4 secretion, consistent with a Th type 2 (Th2) response.
75 10757021 Antitumor immunity was enhanced when the CEA and IL-12 plasmids were coinjected at the same muscle site, but not at separate sites despite increased serum IL-12 levels.
76 10873071 Induction of CEA-specific T-cell precursors was assessed by an ELISPOT assay looking for the production of IFN-gamma.
77 10873071 After four vaccinations, patients who were HLA-A-2-positive demonstrated increases in their CEA-specific T-cell precursor frequencies to a CEA-A2-binding peptide from baseline.
78 10873071 Induction of CEA-specific T-cell precursors was assessed by an ELISPOT assay looking for the production of IFN-gamma.
79 10873071 After four vaccinations, patients who were HLA-A-2-positive demonstrated increases in their CEA-specific T-cell precursor frequencies to a CEA-A2-binding peptide from baseline.
80 11021590 To analyze immune requirements, we immunized gene knockout (KO) mice of C57BL/6 background, deficient in either CD3, CD4, CD8, interferon gamma (IFNgamma), perforin or Fas ligand (FasL).
81 11021590 Only CD3+ mice expressing both CD4 and CD8, which appear equally important, as well as IFNgamma and perforin, could fully resist a tumor challenge.
82 11021590 CEA-stimulated IFNgamma production occurred in both CD4- or CD8-KO mice and in both cases was augmented by IL-12.
83 11049990 Here we provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DCs pulsed with HER-2/neu- or MUC1-derived peptides.
84 11049990 The major CTL response in vivo was induced with the HER-2/neu-derived E75 and the MUC1-derived M1.2 peptide, which lasted for more than 6 months, suggesting that these peptides might be immunodominant.
85 11049990 In addition, in one patient vaccinated with the MUC1-derived peptides, CEA- and MAGE-3 peptide-specific T-cell responses were detected after several vaccinations.
86 11049990 In a second patient immunized with the HER-2/neu peptides, MUC1-specific T lymphocytes were induced after 7 immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antigen.
87 11092617 Three patients experienced clinically stable disease that correlated with increasing CEA-specific precursor T cells, as shown by in vitro interferon-gamma enzyme-linked immunoassay spot tests (ELISPOT).
88 11129322 An enzyme-linked immunosorbent spot (ELISPOT) assay for interferon gamma production has been used to analyze specific T cell responses to a Flu 9-mer peptide, and a 9-mer peptide of carcinoembryonic antigen (CEA).
89 11155821 Vaccination with a mixed vaccine of autogenous and allogeneic breast cancer cells and tumor associated antigens CA15-3, CEA and CA125--results in immune and clinical responses in breast cancer patients.
90 11155821 In this study, we used a multi-antigen vaccine, which included the following antigens: autologous breast cancer cells (AUTOC), allogeneic breast cancer MCF-7 cells (ALLOC), and the tumor associated antigens CA15-3, CEA and CA125, plus low doses of granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2).
91 11155821 Their lymphocyte proliferative responses to AUTOC, ALLOC, CA15-3, CEA and CA125 were tested in lymphocyte blastogenesis assays (LBA) before and after vaccination.
92 11155821 The disease stage and serum CA15-3, CEA and CA125 concentrations were also determined pre- and post-vaccination.
93 11155821 The vaccine induced a significant increase in post-vaccination lymphocyte proliferative responses to AUTOC, CA15-3, CEA and CA125 but not ALLOC, compared to pre-vaccination (p < 0.05, p < 0.01, p < 0.05, p < 0.01 and p > 0.05, respectively, a paired t Test).
94 11155821 We did not find vaccination significantly reduced serum tumor markers CA15-3, CEA and CA125 of these breast cancer patients.
95 11155821 These results suggest that the vaccine mixture of autologous and allogeneic breast cancer cells and tumor associated antigens plus GM-CSF and IL-2 can be administered safely to breast cancer patients and there is evidence for improved immunity and clinical efficacy.
96 11155821 Vaccination with a mixed vaccine of autogenous and allogeneic breast cancer cells and tumor associated antigens CA15-3, CEA and CA125--results in immune and clinical responses in breast cancer patients.
97 11155821 In this study, we used a multi-antigen vaccine, which included the following antigens: autologous breast cancer cells (AUTOC), allogeneic breast cancer MCF-7 cells (ALLOC), and the tumor associated antigens CA15-3, CEA and CA125, plus low doses of granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2).
98 11155821 Their lymphocyte proliferative responses to AUTOC, ALLOC, CA15-3, CEA and CA125 were tested in lymphocyte blastogenesis assays (LBA) before and after vaccination.
99 11155821 The disease stage and serum CA15-3, CEA and CA125 concentrations were also determined pre- and post-vaccination.
100 11155821 The vaccine induced a significant increase in post-vaccination lymphocyte proliferative responses to AUTOC, CA15-3, CEA and CA125 but not ALLOC, compared to pre-vaccination (p < 0.05, p < 0.01, p < 0.05, p < 0.01 and p > 0.05, respectively, a paired t Test).
101 11155821 We did not find vaccination significantly reduced serum tumor markers CA15-3, CEA and CA125 of these breast cancer patients.
102 11155821 These results suggest that the vaccine mixture of autologous and allogeneic breast cancer cells and tumor associated antigens plus GM-CSF and IL-2 can be administered safely to breast cancer patients and there is evidence for improved immunity and clinical efficacy.
103 11155821 Vaccination with a mixed vaccine of autogenous and allogeneic breast cancer cells and tumor associated antigens CA15-3, CEA and CA125--results in immune and clinical responses in breast cancer patients.
104 11155821 In this study, we used a multi-antigen vaccine, which included the following antigens: autologous breast cancer cells (AUTOC), allogeneic breast cancer MCF-7 cells (ALLOC), and the tumor associated antigens CA15-3, CEA and CA125, plus low doses of granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2).
105 11155821 Their lymphocyte proliferative responses to AUTOC, ALLOC, CA15-3, CEA and CA125 were tested in lymphocyte blastogenesis assays (LBA) before and after vaccination.
106 11155821 The disease stage and serum CA15-3, CEA and CA125 concentrations were also determined pre- and post-vaccination.
107 11155821 The vaccine induced a significant increase in post-vaccination lymphocyte proliferative responses to AUTOC, CA15-3, CEA and CA125 but not ALLOC, compared to pre-vaccination (p < 0.05, p < 0.01, p < 0.05, p < 0.01 and p > 0.05, respectively, a paired t Test).
108 11155821 We did not find vaccination significantly reduced serum tumor markers CA15-3, CEA and CA125 of these breast cancer patients.
109 11155821 These results suggest that the vaccine mixture of autologous and allogeneic breast cancer cells and tumor associated antigens plus GM-CSF and IL-2 can be administered safely to breast cancer patients and there is evidence for improved immunity and clinical efficacy.
110 11155821 Vaccination with a mixed vaccine of autogenous and allogeneic breast cancer cells and tumor associated antigens CA15-3, CEA and CA125--results in immune and clinical responses in breast cancer patients.
111 11155821 In this study, we used a multi-antigen vaccine, which included the following antigens: autologous breast cancer cells (AUTOC), allogeneic breast cancer MCF-7 cells (ALLOC), and the tumor associated antigens CA15-3, CEA and CA125, plus low doses of granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2).
112 11155821 Their lymphocyte proliferative responses to AUTOC, ALLOC, CA15-3, CEA and CA125 were tested in lymphocyte blastogenesis assays (LBA) before and after vaccination.
113 11155821 The disease stage and serum CA15-3, CEA and CA125 concentrations were also determined pre- and post-vaccination.
114 11155821 The vaccine induced a significant increase in post-vaccination lymphocyte proliferative responses to AUTOC, CA15-3, CEA and CA125 but not ALLOC, compared to pre-vaccination (p < 0.05, p < 0.01, p < 0.05, p < 0.01 and p > 0.05, respectively, a paired t Test).
115 11155821 We did not find vaccination significantly reduced serum tumor markers CA15-3, CEA and CA125 of these breast cancer patients.
116 11155821 These results suggest that the vaccine mixture of autologous and allogeneic breast cancer cells and tumor associated antigens plus GM-CSF and IL-2 can be administered safely to breast cancer patients and there is evidence for improved immunity and clinical efficacy.
117 11155821 Vaccination with a mixed vaccine of autogenous and allogeneic breast cancer cells and tumor associated antigens CA15-3, CEA and CA125--results in immune and clinical responses in breast cancer patients.
118 11155821 In this study, we used a multi-antigen vaccine, which included the following antigens: autologous breast cancer cells (AUTOC), allogeneic breast cancer MCF-7 cells (ALLOC), and the tumor associated antigens CA15-3, CEA and CA125, plus low doses of granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2).
119 11155821 Their lymphocyte proliferative responses to AUTOC, ALLOC, CA15-3, CEA and CA125 were tested in lymphocyte blastogenesis assays (LBA) before and after vaccination.
120 11155821 The disease stage and serum CA15-3, CEA and CA125 concentrations were also determined pre- and post-vaccination.
121 11155821 The vaccine induced a significant increase in post-vaccination lymphocyte proliferative responses to AUTOC, CA15-3, CEA and CA125 but not ALLOC, compared to pre-vaccination (p < 0.05, p < 0.01, p < 0.05, p < 0.01 and p > 0.05, respectively, a paired t Test).
122 11155821 We did not find vaccination significantly reduced serum tumor markers CA15-3, CEA and CA125 of these breast cancer patients.
123 11155821 These results suggest that the vaccine mixture of autologous and allogeneic breast cancer cells and tumor associated antigens plus GM-CSF and IL-2 can be administered safely to breast cancer patients and there is evidence for improved immunity and clinical efficacy.
124 11155821 Vaccination with a mixed vaccine of autogenous and allogeneic breast cancer cells and tumor associated antigens CA15-3, CEA and CA125--results in immune and clinical responses in breast cancer patients.
125 11155821 In this study, we used a multi-antigen vaccine, which included the following antigens: autologous breast cancer cells (AUTOC), allogeneic breast cancer MCF-7 cells (ALLOC), and the tumor associated antigens CA15-3, CEA and CA125, plus low doses of granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interleukin 2 (IL-2).
126 11155821 Their lymphocyte proliferative responses to AUTOC, ALLOC, CA15-3, CEA and CA125 were tested in lymphocyte blastogenesis assays (LBA) before and after vaccination.
127 11155821 The disease stage and serum CA15-3, CEA and CA125 concentrations were also determined pre- and post-vaccination.
128 11155821 The vaccine induced a significant increase in post-vaccination lymphocyte proliferative responses to AUTOC, CA15-3, CEA and CA125 but not ALLOC, compared to pre-vaccination (p < 0.05, p < 0.01, p < 0.05, p < 0.01 and p > 0.05, respectively, a paired t Test).
129 11155821 We did not find vaccination significantly reduced serum tumor markers CA15-3, CEA and CA125 of these breast cancer patients.
130 11155821 These results suggest that the vaccine mixture of autologous and allogeneic breast cancer cells and tumor associated antigens plus GM-CSF and IL-2 can be administered safely to breast cancer patients and there is evidence for improved immunity and clinical efficacy.
131 11160713 This protein induced extensive syncytia in cells expressing the normal virus receptor CD46 and also in CD46-negative cells expressing the targeted receptor, human CEA.
132 11160713 Replication-competent MV with H replaced by H displaying the long-linker form of scAb was recovered and replicated efficiently in both CD46-positive and CD46-negative, CEA-positive cells.
133 11160713 This protein induced extensive syncytia in cells expressing the normal virus receptor CD46 and also in CD46-negative cells expressing the targeted receptor, human CEA.
134 11160713 Replication-competent MV with H replaced by H displaying the long-linker form of scAb was recovered and replicated efficiently in both CD46-positive and CD46-negative, CEA-positive cells.
135 11196163 Recombinant avian poxviruses [fowlpox and canarypox (ALVAC)], restricted for replication in nonavian cell substrates and expressing granulocyte/macrophage-colony stimulating factor (avipox-GM-CSF), were evaluated for their ability to enrich an immunization site with antigen-presenting cells (APCs) and, in turn, function as biological vaccine adjuvants.
136 11196163 The coadministration of recombinant avipox viruses expressing CEA and GM-CSF significantly enhanced CEA-specific host immunity with an accompanying immunotherapeutic response in tumor-bearing CEA.Tg mice.
137 11196163 Nonetheless, the present findings demonstrate: (a) the effective delivery of GM-CSF to an immunization site using a recombinant avian poxvirus; (b) the compatibility of delivering an antigen and GM-CSF in replication-defective viruses to enhance antigen-specific immunity; and (c) the combined use of recombinant avipox viruses expressing CEA and GM-CSF to generate antitumor immunity directed at a self tumor antigen.
138 11196163 Recombinant avian poxviruses [fowlpox and canarypox (ALVAC)], restricted for replication in nonavian cell substrates and expressing granulocyte/macrophage-colony stimulating factor (avipox-GM-CSF), were evaluated for their ability to enrich an immunization site with antigen-presenting cells (APCs) and, in turn, function as biological vaccine adjuvants.
139 11196163 The coadministration of recombinant avipox viruses expressing CEA and GM-CSF significantly enhanced CEA-specific host immunity with an accompanying immunotherapeutic response in tumor-bearing CEA.Tg mice.
140 11196163 Nonetheless, the present findings demonstrate: (a) the effective delivery of GM-CSF to an immunization site using a recombinant avian poxvirus; (b) the compatibility of delivering an antigen and GM-CSF in replication-defective viruses to enhance antigen-specific immunity; and (c) the combined use of recombinant avipox viruses expressing CEA and GM-CSF to generate antitumor immunity directed at a self tumor antigen.
141 11277324 Treatment with 5-fluorouracil (5-FU) or recombinant interferon-gamma (IFN), alone or in combination, was found to increase carcinoembryonic antigen (CEA) expression in several carcinoma cell lines.
142 11277324 The results showed that exposure of cancer cells to 5-FU or to IFN resulted in increased CEA levels in terms of percentage of CEA-positive cells and mean fluorescence values, as indicated by FACS analysis.
143 11277324 Treatment with 5-fluorouracil (5-FU) or recombinant interferon-gamma (IFN), alone or in combination, was found to increase carcinoembryonic antigen (CEA) expression in several carcinoma cell lines.
144 11277324 The results showed that exposure of cancer cells to 5-FU or to IFN resulted in increased CEA levels in terms of percentage of CEA-positive cells and mean fluorescence values, as indicated by FACS analysis.
145 11300483 Activation of these T cells was indicated by increased secretion of proinflammatory cytokines IFN-gamma, interleukin (IL)-12 and granulocyte/macrophage-colony stimulating factor, as well as specific tumor rejection and growth suppression in vaccinated CEA-transgenic mice after a lethal challenge with murine MC38 colon carcinoma cells.
146 11300483 These tumor cells were double transfected with CEA and the human epithelial cell adhesion molecule (Ep-CAM)/KSA and consequently served as a docking site for a recombinant antibody-IL2 fusion protein (KS1/4-IL2) recognizing KSA.
147 11300483 Importantly, the efficacy of the tumor-protective immune response was markedly increased by boosts with this antibody-IL2 fusion protein, resulting in more effective tumor rejection coupled with increased expression of costimulatory molecules B7.2/B7.2 and intercellular adhesion molecule 1 (ICAM-1) on dendritic cells and intensified release of proinflammatory cytokines IFN-gamma, IL-12, and granulocyte/macrophage-colony stimulating factor from T cells of successfully vaccinated CEA-transgenic C57BL/6J mice.
148 11300483 Increased T-cell activation mediated by boosts with KS1/4-IL2 fusion protein after tumor cell challenge was further indicated by expanded expression of T-cell activation markers CD25, CD28, CD69, and LFA-1.
149 11300483 Activation of these T cells was indicated by increased secretion of proinflammatory cytokines IFN-gamma, interleukin (IL)-12 and granulocyte/macrophage-colony stimulating factor, as well as specific tumor rejection and growth suppression in vaccinated CEA-transgenic mice after a lethal challenge with murine MC38 colon carcinoma cells.
150 11300483 These tumor cells were double transfected with CEA and the human epithelial cell adhesion molecule (Ep-CAM)/KSA and consequently served as a docking site for a recombinant antibody-IL2 fusion protein (KS1/4-IL2) recognizing KSA.
151 11300483 Importantly, the efficacy of the tumor-protective immune response was markedly increased by boosts with this antibody-IL2 fusion protein, resulting in more effective tumor rejection coupled with increased expression of costimulatory molecules B7.2/B7.2 and intercellular adhesion molecule 1 (ICAM-1) on dendritic cells and intensified release of proinflammatory cytokines IFN-gamma, IL-12, and granulocyte/macrophage-colony stimulating factor from T cells of successfully vaccinated CEA-transgenic C57BL/6J mice.
152 11300483 Increased T-cell activation mediated by boosts with KS1/4-IL2 fusion protein after tumor cell challenge was further indicated by expanded expression of T-cell activation markers CD25, CD28, CD69, and LFA-1.
153 11300483 Activation of these T cells was indicated by increased secretion of proinflammatory cytokines IFN-gamma, interleukin (IL)-12 and granulocyte/macrophage-colony stimulating factor, as well as specific tumor rejection and growth suppression in vaccinated CEA-transgenic mice after a lethal challenge with murine MC38 colon carcinoma cells.
154 11300483 These tumor cells were double transfected with CEA and the human epithelial cell adhesion molecule (Ep-CAM)/KSA and consequently served as a docking site for a recombinant antibody-IL2 fusion protein (KS1/4-IL2) recognizing KSA.
155 11300483 Importantly, the efficacy of the tumor-protective immune response was markedly increased by boosts with this antibody-IL2 fusion protein, resulting in more effective tumor rejection coupled with increased expression of costimulatory molecules B7.2/B7.2 and intercellular adhesion molecule 1 (ICAM-1) on dendritic cells and intensified release of proinflammatory cytokines IFN-gamma, IL-12, and granulocyte/macrophage-colony stimulating factor from T cells of successfully vaccinated CEA-transgenic C57BL/6J mice.
156 11300483 Increased T-cell activation mediated by boosts with KS1/4-IL2 fusion protein after tumor cell challenge was further indicated by expanded expression of T-cell activation markers CD25, CD28, CD69, and LFA-1.
157 11350882 The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma.
158 11350882 Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to be an effective vaccine adjuvant because it enhances antigen processing and presentation by dendritic cells.
159 11350882 After an initial dose escalation phase, this study evaluated vaccination with 4.5 x 10(8) plaque-forming units ALVAC-CEA B7.1 alone (n = 30) or with GM-CSF (n = 30) in patients with advanced CEA-expressing tumors to determine whether the addition of the adjuvant GM-CSF enhances induction of CEA-specific T-cells.
160 11350882 Induction of peripheral blood CEA-specific T-cell precursors was assessed in HLA-A2 positive patients by an ELISPOT assay looking for the production of IFN-gamma.
161 11350882 However, the GM-CSF plus vaccine cohort of HLA-A2 positive did not demonstrate a statistically significant increase in their CEA-specific T-cell precursor frequencies compared with baseline results.
162 11350882 ALVAC-CEA B7.1 is safe in patients with advanced, recurrent adenocarcinomas that express CEA, is associated with the induction of a CEA-specific T-cell response in patients treated with vaccine alone but not with vaccine and GM-CSF, and can lead to disease stabilization for up to 13 months.
163 11350882 The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma.
164 11350882 Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to be an effective vaccine adjuvant because it enhances antigen processing and presentation by dendritic cells.
165 11350882 After an initial dose escalation phase, this study evaluated vaccination with 4.5 x 10(8) plaque-forming units ALVAC-CEA B7.1 alone (n = 30) or with GM-CSF (n = 30) in patients with advanced CEA-expressing tumors to determine whether the addition of the adjuvant GM-CSF enhances induction of CEA-specific T-cells.
166 11350882 Induction of peripheral blood CEA-specific T-cell precursors was assessed in HLA-A2 positive patients by an ELISPOT assay looking for the production of IFN-gamma.
167 11350882 However, the GM-CSF plus vaccine cohort of HLA-A2 positive did not demonstrate a statistically significant increase in their CEA-specific T-cell precursor frequencies compared with baseline results.
168 11350882 ALVAC-CEA B7.1 is safe in patients with advanced, recurrent adenocarcinomas that express CEA, is associated with the induction of a CEA-specific T-cell response in patients treated with vaccine alone but not with vaccine and GM-CSF, and can lead to disease stabilization for up to 13 months.
169 11350882 The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma.
170 11350882 Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to be an effective vaccine adjuvant because it enhances antigen processing and presentation by dendritic cells.
171 11350882 After an initial dose escalation phase, this study evaluated vaccination with 4.5 x 10(8) plaque-forming units ALVAC-CEA B7.1 alone (n = 30) or with GM-CSF (n = 30) in patients with advanced CEA-expressing tumors to determine whether the addition of the adjuvant GM-CSF enhances induction of CEA-specific T-cells.
172 11350882 Induction of peripheral blood CEA-specific T-cell precursors was assessed in HLA-A2 positive patients by an ELISPOT assay looking for the production of IFN-gamma.
173 11350882 However, the GM-CSF plus vaccine cohort of HLA-A2 positive did not demonstrate a statistically significant increase in their CEA-specific T-cell precursor frequencies compared with baseline results.
174 11350882 ALVAC-CEA B7.1 is safe in patients with advanced, recurrent adenocarcinomas that express CEA, is associated with the induction of a CEA-specific T-cell response in patients treated with vaccine alone but not with vaccine and GM-CSF, and can lead to disease stabilization for up to 13 months.
175 11350882 The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma.
176 11350882 Granulocyte macrophage colony-stimulating factor (GM-CSF) has been shown to be an effective vaccine adjuvant because it enhances antigen processing and presentation by dendritic cells.
177 11350882 After an initial dose escalation phase, this study evaluated vaccination with 4.5 x 10(8) plaque-forming units ALVAC-CEA B7.1 alone (n = 30) or with GM-CSF (n = 30) in patients with advanced CEA-expressing tumors to determine whether the addition of the adjuvant GM-CSF enhances induction of CEA-specific T-cells.
178 11350882 Induction of peripheral blood CEA-specific T-cell precursors was assessed in HLA-A2 positive patients by an ELISPOT assay looking for the production of IFN-gamma.
179 11350882 However, the GM-CSF plus vaccine cohort of HLA-A2 positive did not demonstrate a statistically significant increase in their CEA-specific T-cell precursor frequencies compared with baseline results.
180 11350882 ALVAC-CEA B7.1 is safe in patients with advanced, recurrent adenocarcinomas that express CEA, is associated with the induction of a CEA-specific T-cell response in patients treated with vaccine alone but not with vaccine and GM-CSF, and can lead to disease stabilization for up to 13 months.
181 11389081 The studies reported here demonstrate: (a) A recombinant avipox (fowlpox, rF) vector expressing the signal 1 (CEA) and the B7-1 costimulatory molecule transgenes (designated rF-CEA/B7-1) is more potent in inducing CEA-specific T-cell responses than rF-CEA; one administration of recombinant fowlpox vector expressing CEA and three different costimulatory molecule transgenes (B7-1, ICAM-1, LFA-3, designated rF-CEA/TRICOM) was more potent in inducing CEA-specific T-cell responses than four vaccinations with rF-CEA or two vaccinations with rF-CEA/B7-1.
182 11389081 (c) The addition of granulocyte macrophage colony-stimulating factor (GM-CSF) to the rF-CEA or rF-CEA/TRICOM vaccinations via the simultaneous administration of a rF-GM-CSF vector enhanced CEA-specific T-cell responses.
183 11389081 These strategies (TRICOM/diversified prime and boost/GM-CSF) were combined to treat CEA-expressing carcinoma liver metastases in CEA-transgenic mice; vaccination was initiated 14 days posttumor transplant.
184 11389081 Antitumor effects in terms of survival and CD8(+) and CD4(+) responses specific for CEA were also observed in this CEA-transgenic mouse model.
185 11389081 The studies reported here demonstrate: (a) A recombinant avipox (fowlpox, rF) vector expressing the signal 1 (CEA) and the B7-1 costimulatory molecule transgenes (designated rF-CEA/B7-1) is more potent in inducing CEA-specific T-cell responses than rF-CEA; one administration of recombinant fowlpox vector expressing CEA and three different costimulatory molecule transgenes (B7-1, ICAM-1, LFA-3, designated rF-CEA/TRICOM) was more potent in inducing CEA-specific T-cell responses than four vaccinations with rF-CEA or two vaccinations with rF-CEA/B7-1.
186 11389081 (c) The addition of granulocyte macrophage colony-stimulating factor (GM-CSF) to the rF-CEA or rF-CEA/TRICOM vaccinations via the simultaneous administration of a rF-GM-CSF vector enhanced CEA-specific T-cell responses.
187 11389081 These strategies (TRICOM/diversified prime and boost/GM-CSF) were combined to treat CEA-expressing carcinoma liver metastases in CEA-transgenic mice; vaccination was initiated 14 days posttumor transplant.
188 11389081 Antitumor effects in terms of survival and CD8(+) and CD4(+) responses specific for CEA were also observed in this CEA-transgenic mouse model.
189 11389081 The studies reported here demonstrate: (a) A recombinant avipox (fowlpox, rF) vector expressing the signal 1 (CEA) and the B7-1 costimulatory molecule transgenes (designated rF-CEA/B7-1) is more potent in inducing CEA-specific T-cell responses than rF-CEA; one administration of recombinant fowlpox vector expressing CEA and three different costimulatory molecule transgenes (B7-1, ICAM-1, LFA-3, designated rF-CEA/TRICOM) was more potent in inducing CEA-specific T-cell responses than four vaccinations with rF-CEA or two vaccinations with rF-CEA/B7-1.
190 11389081 (c) The addition of granulocyte macrophage colony-stimulating factor (GM-CSF) to the rF-CEA or rF-CEA/TRICOM vaccinations via the simultaneous administration of a rF-GM-CSF vector enhanced CEA-specific T-cell responses.
191 11389081 These strategies (TRICOM/diversified prime and boost/GM-CSF) were combined to treat CEA-expressing carcinoma liver metastases in CEA-transgenic mice; vaccination was initiated 14 days posttumor transplant.
192 11389081 Antitumor effects in terms of survival and CD8(+) and CD4(+) responses specific for CEA were also observed in this CEA-transgenic mouse model.
193 11389081 The studies reported here demonstrate: (a) A recombinant avipox (fowlpox, rF) vector expressing the signal 1 (CEA) and the B7-1 costimulatory molecule transgenes (designated rF-CEA/B7-1) is more potent in inducing CEA-specific T-cell responses than rF-CEA; one administration of recombinant fowlpox vector expressing CEA and three different costimulatory molecule transgenes (B7-1, ICAM-1, LFA-3, designated rF-CEA/TRICOM) was more potent in inducing CEA-specific T-cell responses than four vaccinations with rF-CEA or two vaccinations with rF-CEA/B7-1.
194 11389081 (c) The addition of granulocyte macrophage colony-stimulating factor (GM-CSF) to the rF-CEA or rF-CEA/TRICOM vaccinations via the simultaneous administration of a rF-GM-CSF vector enhanced CEA-specific T-cell responses.
195 11389081 These strategies (TRICOM/diversified prime and boost/GM-CSF) were combined to treat CEA-expressing carcinoma liver metastases in CEA-transgenic mice; vaccination was initiated 14 days posttumor transplant.
196 11389081 Antitumor effects in terms of survival and CD8(+) and CD4(+) responses specific for CEA were also observed in this CEA-transgenic mouse model.
197 11418309 In vivo transfection and/or cross-priming of dendritic cells following DNA and adenoviral immunizations for immunotherapy of cancer--changes in peripheral mononuclear subsets and intracellular IL-4 and IFN-gamma lymphokine profile.
198 11418309 One approach is to genetically manipulate tumor cells to either secrete lymphokines (GM-CSF, IL-12, IL-15) or express membrane bound molecules (CD80, CD86).
199 11418309 We have successfully completed a phase I and phase II clinical trials on immunotherapy of prostate cancer using naked DNA and adenoviral immunizations against the prostate-specific membrane antigen (PSMA) and phase I clinical trial on colorectal cancer using naked DNA immunization against the carcinoembryonic antigen (CEA).
200 11427731 Immunization with these antigen-loaded DCs induced CD8 cytotoxic T lymphocytes that recognized tumor cells expressing endogenous CEA.
201 11427731 Staining with peptide-MHC tetramers demonstrated the expansion of CD8 T cells that recognize both the native and altered epitopes and possess an effector cytotoxic T lymphocyte phenotype (CD45RA(+)CD27(-)CCR7(-)).
202 11591784 A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity against colon cancer in carcinoembryonic antigen-transgenic mice.
203 11591784 A carcinoembryonic Ag (CEA)-based DNA vaccine encoding both CEA and CD40 ligand trimer achieved effective tumor-protective immunity against murine colon carcinoma in CEA-transgenic mice by activating both naive T cells and dendritic cells.
204 11591784 Peripheral T cell tolerance to CEA was broken in a prophylactic model by this novel, dual-function DNA vaccine, whose efficacy was further enhanced by boosts with a recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2).
205 11591784 Second, specific activation of dendritic cells was indicated by their marked up-regulation in expression of costimulatory molecules B7.1 (CD80), B7.2 (CD86), and ICAM-1.
206 11591784 Third, a decisive increase over control values was observed in both MHC class I Ag-restricted cytotoxicity of CTLs from successfully vaccinated mice and secretion of proinflammatory cytokines IFN-gamma and IL-12.
207 11591784 Fourth, activation of CTLs was augmented, as indicated by up-regulation of activity markers LFA-1, CD25, CD28, and CD69.
208 11591784 Taken together, these results suggest that a dual-function DNA vaccine encoding CEA and CD40 ligand trimer combined with tumor-targeted IL-2 may be a promising strategy for the rational development of DNA-based cancer vaccines for future clinical applications.
209 11591784 A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity against colon cancer in carcinoembryonic antigen-transgenic mice.
210 11591784 A carcinoembryonic Ag (CEA)-based DNA vaccine encoding both CEA and CD40 ligand trimer achieved effective tumor-protective immunity against murine colon carcinoma in CEA-transgenic mice by activating both naive T cells and dendritic cells.
211 11591784 Peripheral T cell tolerance to CEA was broken in a prophylactic model by this novel, dual-function DNA vaccine, whose efficacy was further enhanced by boosts with a recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2).
212 11591784 Second, specific activation of dendritic cells was indicated by their marked up-regulation in expression of costimulatory molecules B7.1 (CD80), B7.2 (CD86), and ICAM-1.
213 11591784 Third, a decisive increase over control values was observed in both MHC class I Ag-restricted cytotoxicity of CTLs from successfully vaccinated mice and secretion of proinflammatory cytokines IFN-gamma and IL-12.
214 11591784 Fourth, activation of CTLs was augmented, as indicated by up-regulation of activity markers LFA-1, CD25, CD28, and CD69.
215 11591784 Taken together, these results suggest that a dual-function DNA vaccine encoding CEA and CD40 ligand trimer combined with tumor-targeted IL-2 may be a promising strategy for the rational development of DNA-based cancer vaccines for future clinical applications.
216 11591784 A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity against colon cancer in carcinoembryonic antigen-transgenic mice.
217 11591784 A carcinoembryonic Ag (CEA)-based DNA vaccine encoding both CEA and CD40 ligand trimer achieved effective tumor-protective immunity against murine colon carcinoma in CEA-transgenic mice by activating both naive T cells and dendritic cells.
218 11591784 Peripheral T cell tolerance to CEA was broken in a prophylactic model by this novel, dual-function DNA vaccine, whose efficacy was further enhanced by boosts with a recombinant Ab-IL-2 fusion protein (huKS1/4-IL-2).
219 11591784 Second, specific activation of dendritic cells was indicated by their marked up-regulation in expression of costimulatory molecules B7.1 (CD80), B7.2 (CD86), and ICAM-1.
220 11591784 Third, a decisive increase over control values was observed in both MHC class I Ag-restricted cytotoxicity of CTLs from successfully vaccinated mice and secretion of proinflammatory cytokines IFN-gamma and IL-12.
221 11591784 Fourth, activation of CTLs was augmented, as indicated by up-regulation of activity markers LFA-1, CD25, CD28, and CD69.
222 11591784 Taken together, these results suggest that a dual-function DNA vaccine encoding CEA and CD40 ligand trimer combined with tumor-targeted IL-2 may be a promising strategy for the rational development of DNA-based cancer vaccines for future clinical applications.
223 11731437 A new murine model of human colorectal cancer was generated by crossing human carcinoembryonic antigen (CEA) transgenic mice (H-2K(b)) with adenomatous polyposis coli (Apc1638N) knockout mice (H-2K(b)).
224 11904734 The authors performed a clinical study of a vaccine using autologous dendritic cells (DCs) pulsed with CEA652 and adjuvant cytokines, natural human interferon alpha (nhuIFN-alpha), and natural human tumor necrosis factor alpha (nhuTNF-alpha), for the treatment of patients with CEA-expressing advanced metastatic malignancies.
225 11904734 DCs were generated from plastic adherent monocytes of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (PBMCs) in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4).
226 12100028 The cell lines expressed HLA-A2 as well as shared tumour-associated antigens (TAAs) representative of colon carcinomas: CEA, Ep-CAM, MUC1, HER2/neu and MAGE antigens.
227 12100028 They did not secrete high levels of the immunosuppressive factors TGF-beta, IL-10 or prostaglandins.
228 12208760 Cell surface expression of CEA was low for the SCC lines; however, there was moderate to strong cytoplasmic staining intensity for all of the CEA(+) HNC lines by immunocytochemistry.
229 12208760 Additional supportive evidence for CEA as a target was demonstrated by the presence of cytolytic activity of an HLA-A2-restricted/CEA-epitope-specific human CTL against a CEA-overexpressing HNC-derived SCC line.
230 12208760 Cell surface expression of CEA was low for the SCC lines; however, there was moderate to strong cytoplasmic staining intensity for all of the CEA(+) HNC lines by immunocytochemistry.
231 12208760 Additional supportive evidence for CEA as a target was demonstrated by the presence of cytolytic activity of an HLA-A2-restricted/CEA-epitope-specific human CTL against a CEA-overexpressing HNC-derived SCC line.
232 12208761 Identification of an interferon-gamma-inducible carcinoembryonic antigen (CEA) CD8(+) T-cell epitope, which mediates tumor killing in CEA transgenic mice.
233 12208761 This study describes a CD8(+) T-cell line specific for a MHC class I-restricted carcinoembryonic antigen (CEA) epitope, residues 526-533, isolated from CEA transgenic (CEA.Tg) mice immunized with a recombinant vaccinia-CEA vaccine.
234 12208761 Incubation of splenocytes from the immune CEA.Tg mice with the CEA(526-533) peptide resulted in the outgrowth of low-avidity CD8(+) T cells, which produced IFN-gamma and mediated perforin-dependent tumor cell lysis.
235 12208761 However, the CEA peptide-specific T cells killed CEA-expressing murine colorectal tumor cells only after pretreatment of the targets with murine IFN-gamma (muIFN-gamma), and lysis was H-2D(b)-restricted and involved the Fas-FasL-mediated cytotoxic pathway.
236 12208761 The results indicate that (a) vaccination of mice carrying the human CEA gene with recombinant vaccinia-CEA generates a CEA epitope-specific, CD8-dependent CTL response, (b) CEA, a normal, tissue-specific antigen, can also serve as a target for antitumor immunity after the adoptive transfer of CEA peptide-specific T cells, and (c) muIFN-gamma might be an effective cancer vaccine adjuvant by virtue of its ability to augment the susceptibility of tumor targets to cell-mediated lysis.
237 12208761 Identification of an interferon-gamma-inducible carcinoembryonic antigen (CEA) CD8(+) T-cell epitope, which mediates tumor killing in CEA transgenic mice.
238 12208761 This study describes a CD8(+) T-cell line specific for a MHC class I-restricted carcinoembryonic antigen (CEA) epitope, residues 526-533, isolated from CEA transgenic (CEA.Tg) mice immunized with a recombinant vaccinia-CEA vaccine.
239 12208761 Incubation of splenocytes from the immune CEA.Tg mice with the CEA(526-533) peptide resulted in the outgrowth of low-avidity CD8(+) T cells, which produced IFN-gamma and mediated perforin-dependent tumor cell lysis.
240 12208761 However, the CEA peptide-specific T cells killed CEA-expressing murine colorectal tumor cells only after pretreatment of the targets with murine IFN-gamma (muIFN-gamma), and lysis was H-2D(b)-restricted and involved the Fas-FasL-mediated cytotoxic pathway.
241 12208761 The results indicate that (a) vaccination of mice carrying the human CEA gene with recombinant vaccinia-CEA generates a CEA epitope-specific, CD8-dependent CTL response, (b) CEA, a normal, tissue-specific antigen, can also serve as a target for antitumor immunity after the adoptive transfer of CEA peptide-specific T cells, and (c) muIFN-gamma might be an effective cancer vaccine adjuvant by virtue of its ability to augment the susceptibility of tumor targets to cell-mediated lysis.
242 12208761 Identification of an interferon-gamma-inducible carcinoembryonic antigen (CEA) CD8(+) T-cell epitope, which mediates tumor killing in CEA transgenic mice.
243 12208761 This study describes a CD8(+) T-cell line specific for a MHC class I-restricted carcinoembryonic antigen (CEA) epitope, residues 526-533, isolated from CEA transgenic (CEA.Tg) mice immunized with a recombinant vaccinia-CEA vaccine.
244 12208761 Incubation of splenocytes from the immune CEA.Tg mice with the CEA(526-533) peptide resulted in the outgrowth of low-avidity CD8(+) T cells, which produced IFN-gamma and mediated perforin-dependent tumor cell lysis.
245 12208761 However, the CEA peptide-specific T cells killed CEA-expressing murine colorectal tumor cells only after pretreatment of the targets with murine IFN-gamma (muIFN-gamma), and lysis was H-2D(b)-restricted and involved the Fas-FasL-mediated cytotoxic pathway.
246 12208761 The results indicate that (a) vaccination of mice carrying the human CEA gene with recombinant vaccinia-CEA generates a CEA epitope-specific, CD8-dependent CTL response, (b) CEA, a normal, tissue-specific antigen, can also serve as a target for antitumor immunity after the adoptive transfer of CEA peptide-specific T cells, and (c) muIFN-gamma might be an effective cancer vaccine adjuvant by virtue of its ability to augment the susceptibility of tumor targets to cell-mediated lysis.
247 12208761 Identification of an interferon-gamma-inducible carcinoembryonic antigen (CEA) CD8(+) T-cell epitope, which mediates tumor killing in CEA transgenic mice.
248 12208761 This study describes a CD8(+) T-cell line specific for a MHC class I-restricted carcinoembryonic antigen (CEA) epitope, residues 526-533, isolated from CEA transgenic (CEA.Tg) mice immunized with a recombinant vaccinia-CEA vaccine.
249 12208761 Incubation of splenocytes from the immune CEA.Tg mice with the CEA(526-533) peptide resulted in the outgrowth of low-avidity CD8(+) T cells, which produced IFN-gamma and mediated perforin-dependent tumor cell lysis.
250 12208761 However, the CEA peptide-specific T cells killed CEA-expressing murine colorectal tumor cells only after pretreatment of the targets with murine IFN-gamma (muIFN-gamma), and lysis was H-2D(b)-restricted and involved the Fas-FasL-mediated cytotoxic pathway.
251 12208761 The results indicate that (a) vaccination of mice carrying the human CEA gene with recombinant vaccinia-CEA generates a CEA epitope-specific, CD8-dependent CTL response, (b) CEA, a normal, tissue-specific antigen, can also serve as a target for antitumor immunity after the adoptive transfer of CEA peptide-specific T cells, and (c) muIFN-gamma might be an effective cancer vaccine adjuvant by virtue of its ability to augment the susceptibility of tumor targets to cell-mediated lysis.
252 12208761 Identification of an interferon-gamma-inducible carcinoembryonic antigen (CEA) CD8(+) T-cell epitope, which mediates tumor killing in CEA transgenic mice.
253 12208761 This study describes a CD8(+) T-cell line specific for a MHC class I-restricted carcinoembryonic antigen (CEA) epitope, residues 526-533, isolated from CEA transgenic (CEA.Tg) mice immunized with a recombinant vaccinia-CEA vaccine.
254 12208761 Incubation of splenocytes from the immune CEA.Tg mice with the CEA(526-533) peptide resulted in the outgrowth of low-avidity CD8(+) T cells, which produced IFN-gamma and mediated perforin-dependent tumor cell lysis.
255 12208761 However, the CEA peptide-specific T cells killed CEA-expressing murine colorectal tumor cells only after pretreatment of the targets with murine IFN-gamma (muIFN-gamma), and lysis was H-2D(b)-restricted and involved the Fas-FasL-mediated cytotoxic pathway.
256 12208761 The results indicate that (a) vaccination of mice carrying the human CEA gene with recombinant vaccinia-CEA generates a CEA epitope-specific, CD8-dependent CTL response, (b) CEA, a normal, tissue-specific antigen, can also serve as a target for antitumor immunity after the adoptive transfer of CEA peptide-specific T cells, and (c) muIFN-gamma might be an effective cancer vaccine adjuvant by virtue of its ability to augment the susceptibility of tumor targets to cell-mediated lysis.
257 12350054 We provide evidence that patients with advanced breast and ovarian cancer can be efficiently vaccinated with autologous DC pulsed with HER-2/neu- or MUC1-derived peptides.
258 12350054 In addition, in one patient vaccinated with the MUC1-derived peptides, CEA- and MAGE-3 peptide-specific T-cell responses were detected after several vaccinations.
259 12350054 In a second patient immunized with the HER-2/neu peptides, MUC1-specific T lymphocytes were induced after seven immunizations, suggesting that antigen spreading in vivo might occur after successful immunization with a single tumor antigen.
260 12350054 In this ongoing trial one patient with metastatic RCC developed a partial remission of the metastatic sites was induced after the first four vaccinations with MUC1 peptides pulsed DC, that was ongoing after the next cycles containing IL-2.
261 12378152 A series of phase I/II clinical studies evaluating ALVAC recombinants carrying either the CEA, p53, MAGE1 or MAGE3 genes, administered through the subcutaneous, intradermal or intravenous routes, has shown that this approach is safe and can induce tumor-specific antibody or T cell responses in at least some of the patients.
262 12384537 The vaccines used were recombinant vaccinia virus containing the transgenes for CEA and three T-cell costimulatory molecules [B7-1, ICAM-1, and LFA-3, designated recombinant vaccinia (rV)-CEA/TRICOM], with each transgene under the control of individual poxvirus promoters, and a replication-defective avipox virus (fowlpox; rF) containing the same four transgenes (designated rF-CEA/TRICOM).
263 12384537 The results demonstrate that (a) continued boosting with vaccine is required to maintain CEA-specific T-cell responses, and boosting with rF-CEA/TRICOM is superior to boosting with rF-CEA; (b) a diversified vaccination protocol consisting of primary vaccination with rV-CEA/TRICOM followed by boosting with rF-CEA/TRICOM is more efficacious than homogeneous vaccination with rF-CEA/TRICOM in the induction of both CEA-specific T-cell responses and antitumor activity; and (c) the use of cytokines, local granulocyte macrophage colony-stimulating factor (GM-CSF) and low-dose systemic interleukin 2, in combination with vaccine is essential in inducing antitumor activity, as compared with the use of cytokines alone, or the use of vaccines without cytokine.
264 12384537 Both GM-CSF and interleukin 2 were shown to contribute to the induction of CEA-specific T-cell responses.
265 12384537 The vaccines used were recombinant vaccinia virus containing the transgenes for CEA and three T-cell costimulatory molecules [B7-1, ICAM-1, and LFA-3, designated recombinant vaccinia (rV)-CEA/TRICOM], with each transgene under the control of individual poxvirus promoters, and a replication-defective avipox virus (fowlpox; rF) containing the same four transgenes (designated rF-CEA/TRICOM).
266 12384537 The results demonstrate that (a) continued boosting with vaccine is required to maintain CEA-specific T-cell responses, and boosting with rF-CEA/TRICOM is superior to boosting with rF-CEA; (b) a diversified vaccination protocol consisting of primary vaccination with rV-CEA/TRICOM followed by boosting with rF-CEA/TRICOM is more efficacious than homogeneous vaccination with rF-CEA/TRICOM in the induction of both CEA-specific T-cell responses and antitumor activity; and (c) the use of cytokines, local granulocyte macrophage colony-stimulating factor (GM-CSF) and low-dose systemic interleukin 2, in combination with vaccine is essential in inducing antitumor activity, as compared with the use of cytokines alone, or the use of vaccines without cytokine.
267 12384537 Both GM-CSF and interleukin 2 were shown to contribute to the induction of CEA-specific T-cell responses.
268 12384537 The vaccines used were recombinant vaccinia virus containing the transgenes for CEA and three T-cell costimulatory molecules [B7-1, ICAM-1, and LFA-3, designated recombinant vaccinia (rV)-CEA/TRICOM], with each transgene under the control of individual poxvirus promoters, and a replication-defective avipox virus (fowlpox; rF) containing the same four transgenes (designated rF-CEA/TRICOM).
269 12384537 The results demonstrate that (a) continued boosting with vaccine is required to maintain CEA-specific T-cell responses, and boosting with rF-CEA/TRICOM is superior to boosting with rF-CEA; (b) a diversified vaccination protocol consisting of primary vaccination with rV-CEA/TRICOM followed by boosting with rF-CEA/TRICOM is more efficacious than homogeneous vaccination with rF-CEA/TRICOM in the induction of both CEA-specific T-cell responses and antitumor activity; and (c) the use of cytokines, local granulocyte macrophage colony-stimulating factor (GM-CSF) and low-dose systemic interleukin 2, in combination with vaccine is essential in inducing antitumor activity, as compared with the use of cytokines alone, or the use of vaccines without cytokine.
270 12384537 Both GM-CSF and interleukin 2 were shown to contribute to the induction of CEA-specific T-cell responses.
271 12460911 CEA.Tg mice were crossed with mice bearing a mutation in the Apc gene (MIN mice), and the CEA.Tg/MIN progeny developed multiple intestinal neoplasms, which overexpress CEA to levels that are reminiscent of those reported for tubulovillous intestinal adenomas from patients.
272 12460911 CEA.Tg/MIN mice were vaccinated with an aggressive diversified prime/boost vaccine regimen: (a) a primary vaccine consisting of recombinant vaccinia virus-expressing CEA and a triad of costimulatory molecules (TRICOM): B7.1, ICAM-1, and LFA-3 (rV-CEA-TRICOM); and (b) a booster vaccine using CEA-TRICOM in a recombinant avipox (fowlpox) virus (rF-CEA-TRICOM).
273 12460911 CEA.Tg mice were crossed with mice bearing a mutation in the Apc gene (MIN mice), and the CEA.Tg/MIN progeny developed multiple intestinal neoplasms, which overexpress CEA to levels that are reminiscent of those reported for tubulovillous intestinal adenomas from patients.
274 12460911 CEA.Tg/MIN mice were vaccinated with an aggressive diversified prime/boost vaccine regimen: (a) a primary vaccine consisting of recombinant vaccinia virus-expressing CEA and a triad of costimulatory molecules (TRICOM): B7.1, ICAM-1, and LFA-3 (rV-CEA-TRICOM); and (b) a booster vaccine using CEA-TRICOM in a recombinant avipox (fowlpox) virus (rF-CEA-TRICOM).
275 12487060 Another study examined this issue by studying prostatic acid phosphatase (PAP) protein-loaded mature DCs injected intravenously, intradermally, and intralymphatically in prostate cancer patients [45].
276 12487060 Regardless of route of administration, T cell responses were induced as measured by proliferation when PBMCs in vitro were stimulated with the PAP protein.
277 12487060 A number of studies have demonstrated that maturation signals such as inflammatory cytokines and CD40 ligation lead to down-regulation of antigen processing and up-regulation of the chemokine receptor CCR7, which leads to homing to lymph nodes [46] as well as the MHC molecules, costimulatory molecules, and maturation markers [8,47,48].
278 12487060 One study using CEA peptides and CEA RNA found that optimal T cell presentation occurs when peptides are loaded after maturation with CD40 ligand and when RNA is transfected before maturation with CD40 ligand [53].
279 12487060 Many use DTH responses, but these may measure CD4 T cells instead of CD8 T cells.
280 12487060 Others have monitored the decrease in serum tumor markers such as PSA or CEA.
281 12487060 Another study examined this issue by studying prostatic acid phosphatase (PAP) protein-loaded mature DCs injected intravenously, intradermally, and intralymphatically in prostate cancer patients [45].
282 12487060 Regardless of route of administration, T cell responses were induced as measured by proliferation when PBMCs in vitro were stimulated with the PAP protein.
283 12487060 A number of studies have demonstrated that maturation signals such as inflammatory cytokines and CD40 ligation lead to down-regulation of antigen processing and up-regulation of the chemokine receptor CCR7, which leads to homing to lymph nodes [46] as well as the MHC molecules, costimulatory molecules, and maturation markers [8,47,48].
284 12487060 One study using CEA peptides and CEA RNA found that optimal T cell presentation occurs when peptides are loaded after maturation with CD40 ligand and when RNA is transfected before maturation with CD40 ligand [53].
285 12487060 Many use DTH responses, but these may measure CD4 T cells instead of CD8 T cells.
286 12487060 Others have monitored the decrease in serum tumor markers such as PSA or CEA.
287 12584740 Previous studies have shown that 5-fluorouracil (5-FU) can upregulate the expression of membrane-associated carcino-embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines.
288 12584740 The CEA peptide-specific CTLs generated in our laboratory from normal HLA-A(*)02.01(+) donor PBMCs, were able to kill HLA-A(*)02.01(+)/CEA(+) breast (MCF-7-T103) and colon (HLA-A(*)02.01 gene-transfected HT-29 and C22.20) carcinoma cells in HLA-A(*)02.01 restricted manner.
289 12584740 Previous studies have shown that 5-fluorouracil (5-FU) can upregulate the expression of membrane-associated carcino-embryonic antigen (CEA), and MHC molecules in colon and breast carcinoma cell lines.
290 12584740 The CEA peptide-specific CTLs generated in our laboratory from normal HLA-A(*)02.01(+) donor PBMCs, were able to kill HLA-A(*)02.01(+)/CEA(+) breast (MCF-7-T103) and colon (HLA-A(*)02.01 gene-transfected HT-29 and C22.20) carcinoma cells in HLA-A(*)02.01 restricted manner.
291 12704102 In addition, cross-reactive blocking of OpaB-expressing bacteria to both CEACAM1- and CEA-transfected cells was found for all sera.
292 12782590 Immune-splenic lymphocytes when stimulated in vitro with 3H1 or CEA, showed increased proliferative CD4(+) Th1 type T-cell response and secreted significantly high levels of Th1 cytokines [IFN-gamma, interleukin (IL)-2] and low levels of Th2 cytokines (IL-4, IL-10).
293 12782590 This vaccine also induced MHC class I antigen-restricted CD8(+) T-cell responses.
294 12782590 The up-regulation of activation markers CD69 and CD25 on CD8(+) CTLs correlated with antigen-specific strong CTL responses in vitro.
295 14500642 HLA-A*0201-restricted CD8(+) T cells recognizing Ags expressed in human melanoma (melanoma Ag recognized by T cell-1 (MART-1)/melanoma Ag A (Melan-A)) or colon carcinoma (carcinoembryonic Ag (CEA)/epithelial cell adhesion molecule (EpCAM)) were triggered to release IFN-gamma and to mediate cytotoxic activity by HLA-A*0201-matched APCs pulsed with hsp96 purified from tumor cells expressing the relevant Ag.
296 14500642 Immunization with autologous tumor-derived hsp96 induced a significant increase in the recognition of MART-1/Melan-A(27-35) in three of five HLA-A*0201 melanoma patients, and of CEA(571-579) and EpCAM(263-271) in two of five HLA-A*0201 colon carcinoma patients, respectively, as detected by ELISPOT and HLA/tetramer staining.
297 14500642 HLA-A*0201-restricted CD8(+) T cells recognizing Ags expressed in human melanoma (melanoma Ag recognized by T cell-1 (MART-1)/melanoma Ag A (Melan-A)) or colon carcinoma (carcinoembryonic Ag (CEA)/epithelial cell adhesion molecule (EpCAM)) were triggered to release IFN-gamma and to mediate cytotoxic activity by HLA-A*0201-matched APCs pulsed with hsp96 purified from tumor cells expressing the relevant Ag.
298 14500642 Immunization with autologous tumor-derived hsp96 induced a significant increase in the recognition of MART-1/Melan-A(27-35) in three of five HLA-A*0201 melanoma patients, and of CEA(571-579) and EpCAM(263-271) in two of five HLA-A*0201 colon carcinoma patients, respectively, as detected by ELISPOT and HLA/tetramer staining.
299 14572791 Enhanced expression of lymphotactin by CD8+ T cells is selectively induced by enhancer agonist peptides of tumor-associated antigens.
300 14572791 We compared the gene expression profiles of this CEA-specific CD8 T cell line when (a) stimulated with the native peptide used to derive this line vs. no peptide, and (b) stimulated with its TCR enhancer agonist epitope vs. no peptide.
301 14605762 A baculovirus-produced recombinant CEA (rCEA) protein comprising the extracellular region was used for vaccination of CRC patients with or without GM-CSF as an adjuvant cytokine.
302 14615150 The T-cell lines, primed by the recombinant AdVCEA-infected DCs in vitro, not only recognized CEA peptide-loaded target cells but also CEA-expressing tumor cell lines in a human leukocyte antigen (HLA) class I-restricted manner.
303 14615150 Cytotoxic activity toward target cells was found to be mediated primarily by CD8(+) T-cells, although both CD8(+) cells and CD4(+) cells were able to lyse CEA peptide-loaded target cells.
304 14615150 The T-cell lines, primed by the recombinant AdVCEA-infected DCs in vitro, not only recognized CEA peptide-loaded target cells but also CEA-expressing tumor cell lines in a human leukocyte antigen (HLA) class I-restricted manner.
305 14615150 Cytotoxic activity toward target cells was found to be mediated primarily by CD8(+) T-cells, although both CD8(+) cells and CD4(+) cells were able to lyse CEA peptide-loaded target cells.
306 14617157 Mapping the binding domains on meningococcal Opa proteins for CEACAM1 and CEA receptors.
307 14617157 Neisseria meningitidis strain H44/76 possesses four different Opa proteins, of which OpaA and OpaJ bind to CEACAM1, while OpaB and OpaD bind to CEACAM1 and CEA.
308 14617157 Hybrid Opa variants with different combinations of HV-1 and HV-2 derived from OpaB and OpaJ showed a reduced binding to CEACAM1 and CEA, indicating that particular combinations of HV-1 and HV-2 are required for the Opa binding capacity.
309 14617157 Mapping the binding domains on meningococcal Opa proteins for CEACAM1 and CEA receptors.
310 14617157 Neisseria meningitidis strain H44/76 possesses four different Opa proteins, of which OpaA and OpaJ bind to CEACAM1, while OpaB and OpaD bind to CEACAM1 and CEA.
311 14617157 Hybrid Opa variants with different combinations of HV-1 and HV-2 derived from OpaB and OpaJ showed a reduced binding to CEACAM1 and CEA, indicating that particular combinations of HV-1 and HV-2 are required for the Opa binding capacity.
312 14617157 Mapping the binding domains on meningococcal Opa proteins for CEACAM1 and CEA receptors.
313 14617157 Neisseria meningitidis strain H44/76 possesses four different Opa proteins, of which OpaA and OpaJ bind to CEACAM1, while OpaB and OpaD bind to CEACAM1 and CEA.
314 14617157 Hybrid Opa variants with different combinations of HV-1 and HV-2 derived from OpaB and OpaJ showed a reduced binding to CEACAM1 and CEA, indicating that particular combinations of HV-1 and HV-2 are required for the Opa binding capacity.
315 14633725 Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM).
316 14633725 Vaccination of mice with MVA-CEA/TRICOM induced potent CD4+ and CD8+ T-cell responses specific for CEA.
317 14633725 The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4+ and CD8+ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost.
318 14633725 Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM).
319 14633725 Vaccination of mice with MVA-CEA/TRICOM induced potent CD4+ and CD8+ T-cell responses specific for CEA.
320 14633725 The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4+ and CD8+ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost.
321 14633725 Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM).
322 14633725 Vaccination of mice with MVA-CEA/TRICOM induced potent CD4+ and CD8+ T-cell responses specific for CEA.
323 14633725 The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4+ and CD8+ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost.
324 14679013 However, CEA belongs to the CD66 immunoglobulin super-gene family that comprises highly homologous molecules expressed on leukocytes, making CEA a potential autoantigen expressed on hematopoietic cells.
325 14679013 We used a MHC class II epitope prediction algorithm (TEPITOPE) to select 11 sequence segments of CEA that could form promiscuous CD4(+) T-cell epitopes and used synthetic peptides corresponding to the predicted sequences to propagate in vitro CD4(+) T cells from healthy donors and colon cancer patients.
326 14679013 Cross-recognition experiments with peptide analogues present on the CD66 homologous proteins showed that CEA(177-189/355-367)-specific CD4(+) T cells did not recognize the analogues, demonstrating that recognition of the immunodominant epitope is CEA specific.
327 14679013 These data suggest that the repertoire of CEA(177-189/355-367)-specific CD4(+) T cells might have been shaped by a selective process to exclude CD4(+) T cells specific for CD66 homologues expressed on leukocyte, while preserving the CEA-specific repertoire.
328 14679013 However, CEA belongs to the CD66 immunoglobulin super-gene family that comprises highly homologous molecules expressed on leukocytes, making CEA a potential autoantigen expressed on hematopoietic cells.
329 14679013 We used a MHC class II epitope prediction algorithm (TEPITOPE) to select 11 sequence segments of CEA that could form promiscuous CD4(+) T-cell epitopes and used synthetic peptides corresponding to the predicted sequences to propagate in vitro CD4(+) T cells from healthy donors and colon cancer patients.
330 14679013 Cross-recognition experiments with peptide analogues present on the CD66 homologous proteins showed that CEA(177-189/355-367)-specific CD4(+) T cells did not recognize the analogues, demonstrating that recognition of the immunodominant epitope is CEA specific.
331 14679013 These data suggest that the repertoire of CEA(177-189/355-367)-specific CD4(+) T cells might have been shaped by a selective process to exclude CD4(+) T cells specific for CD66 homologues expressed on leukocyte, while preserving the CEA-specific repertoire.
332 14679013 However, CEA belongs to the CD66 immunoglobulin super-gene family that comprises highly homologous molecules expressed on leukocytes, making CEA a potential autoantigen expressed on hematopoietic cells.
333 14679013 We used a MHC class II epitope prediction algorithm (TEPITOPE) to select 11 sequence segments of CEA that could form promiscuous CD4(+) T-cell epitopes and used synthetic peptides corresponding to the predicted sequences to propagate in vitro CD4(+) T cells from healthy donors and colon cancer patients.
334 14679013 Cross-recognition experiments with peptide analogues present on the CD66 homologous proteins showed that CEA(177-189/355-367)-specific CD4(+) T cells did not recognize the analogues, demonstrating that recognition of the immunodominant epitope is CEA specific.
335 14679013 These data suggest that the repertoire of CEA(177-189/355-367)-specific CD4(+) T cells might have been shaped by a selective process to exclude CD4(+) T cells specific for CD66 homologues expressed on leukocyte, while preserving the CEA-specific repertoire.
336 14679013 However, CEA belongs to the CD66 immunoglobulin super-gene family that comprises highly homologous molecules expressed on leukocytes, making CEA a potential autoantigen expressed on hematopoietic cells.
337 14679013 We used a MHC class II epitope prediction algorithm (TEPITOPE) to select 11 sequence segments of CEA that could form promiscuous CD4(+) T-cell epitopes and used synthetic peptides corresponding to the predicted sequences to propagate in vitro CD4(+) T cells from healthy donors and colon cancer patients.
338 14679013 Cross-recognition experiments with peptide analogues present on the CD66 homologous proteins showed that CEA(177-189/355-367)-specific CD4(+) T cells did not recognize the analogues, demonstrating that recognition of the immunodominant epitope is CEA specific.
339 14679013 These data suggest that the repertoire of CEA(177-189/355-367)-specific CD4(+) T cells might have been shaped by a selective process to exclude CD4(+) T cells specific for CD66 homologues expressed on leukocyte, while preserving the CEA-specific repertoire.
340 14733650 Phase I study of recombinant carcinoembryonic antigen (CEA) vaccinia virus vaccine with post vaccination carcinoembryonic antigen peptide (CAP-1) boost.
341 14735319 In this pilot study, we have used the peptide-pulsed dendritic cells (DCs) generated from peripheral blood mononuclear cells (PBMCs) supplemented with GM-CSF and IL-4 as the source of the vaccine.
342 14735319 Furthermore, A24/CEA peptide tetramer assay revealed an increase in peptide-specific T-cell precursor frequency in vaccinated patients.
343 14998548 (a) detection of tumour cells in the peripheral blood, bone marrow or lymph node using reverse transcriptase-polymerase chain reaction (RT-PCR)-based measurement of CEA mRNA; (b) targeting of anticancer agents or radionuclides by tumour-selective anti-CEA monoclonal antibodies (mAbs); (c) use of antitumour vaccines capable of eliciting major histocompatibility complex (MHC)-restricted immune responses against CEA-derived peptides.
344 14998548 Actually, it has been shown that the expression of CEA can be up-regulated by pharmacological agents including, antineoplastic drugs (i.e. 5-fluorouracil), cytokines (i.e. interferons or interleukin-6), differentiating agents (i.e. sodium butyrate) and protein kinase inhibitors (i.e. staurosporine).
345 14998548 Moreover, the same agents could increase the efficacy of vaccines based on immunogenic CEA-derived peptides restricted by the MHC.
346 14998548 (a) detection of tumour cells in the peripheral blood, bone marrow or lymph node using reverse transcriptase-polymerase chain reaction (RT-PCR)-based measurement of CEA mRNA; (b) targeting of anticancer agents or radionuclides by tumour-selective anti-CEA monoclonal antibodies (mAbs); (c) use of antitumour vaccines capable of eliciting major histocompatibility complex (MHC)-restricted immune responses against CEA-derived peptides.
347 14998548 Actually, it has been shown that the expression of CEA can be up-regulated by pharmacological agents including, antineoplastic drugs (i.e. 5-fluorouracil), cytokines (i.e. interferons or interleukin-6), differentiating agents (i.e. sodium butyrate) and protein kinase inhibitors (i.e. staurosporine).
348 14998548 Moreover, the same agents could increase the efficacy of vaccines based on immunogenic CEA-derived peptides restricted by the MHC.
349 14998548 (a) detection of tumour cells in the peripheral blood, bone marrow or lymph node using reverse transcriptase-polymerase chain reaction (RT-PCR)-based measurement of CEA mRNA; (b) targeting of anticancer agents or radionuclides by tumour-selective anti-CEA monoclonal antibodies (mAbs); (c) use of antitumour vaccines capable of eliciting major histocompatibility complex (MHC)-restricted immune responses against CEA-derived peptides.
350 14998548 Actually, it has been shown that the expression of CEA can be up-regulated by pharmacological agents including, antineoplastic drugs (i.e. 5-fluorouracil), cytokines (i.e. interferons or interleukin-6), differentiating agents (i.e. sodium butyrate) and protein kinase inhibitors (i.e. staurosporine).
351 14998548 Moreover, the same agents could increase the efficacy of vaccines based on immunogenic CEA-derived peptides restricted by the MHC.
352 15003648 Plasmids encoding membrane-bound IL-4 or IL-12 strongly costimulate DNA vaccination against carcinoembryonic antigen (CEA).
353 15003648 We and others have previously shown that plasmids encoding soluble IL-4 and IL-12 are effective adjuvants for DNA vaccination.
354 15102666 Generation of carcinoembryonic antigen (CEA)-specific T-cell responses in HLA-A*0201 and HLA-A*2402 late-stage colorectal cancer patients after vaccination with dendritic cells loaded with CEA peptides.
355 15150127 The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli.
356 15150127 Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN-gamma production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib.
357 15150127 When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the Apc(Delta850) gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2.
358 15161680 Durable carcinoembryonic antigen (CEA)-specific humoral and cellular immune responses in colorectal carcinoma patients vaccinated with recombinant CEA and granulocyte/macrophage colony-stimulating factor.
359 15205348 This was mediated by the engagement of the Fas/Fas ligand pathway because Ag-bearing tumor cells expressing dominant-negative Fas were not susceptible to this combination therapy.
360 15205348 Mice cured of tumors demonstrated CD4(+) and CD8(+) T-cell responses specific for CEA but also revealed the induction of high levels of T-cell responses to two other antigens (gp70 and p53) overexpressed in tumor, indicating the presence of a consequential antigen cascade.
361 15280475 The immunogenic properties of baculovirus as vaccine vector were not restricted to E2 because a CEA-specific CD4(+) T-cell response was observed upon intramuscular injection of Bac-CEA.
362 15280475 Induction of inflammatory cytokines such as gamma interferon, tumor necrosis factor alpha, and interleukin-6 was detected as early as 6 h postinjection of Bac-G-E2.
363 15365776 A CD80-transfected human breast cancer cell variant induces HER-2/neu-specific T cells in HLA-A*02-matched situations in vitro as well as in vivo.
364 15365776 Using CD80+ KS breast cancer cells and human leukocyte antigen (HLA)-A*02-matched peripheral blood mononuclear cells (PBMCs) of breast cancer patients in allogeneic mixed lymphocyte-tumor cell cultures (MLTCs), it was possible to isolate HLA-A*02-restricted cytotoxic T cells (CTLs).
365 15365776 KS breast cancer cells were demonstrated to express already known TAAs such as CEA, MUC-1, MAGE-1, MAGE-2, and MAGE-3.
366 15365776 To further improve antigenicity, HER-2/neu was added to this panel as a marker antigen known to elicit HLA-A*02-restricted CTLs in patients with breast cancer.
367 15365776 Thus, the antigen-processing and antigen-presentation capacity of KS cells was further demonstrated by the stimulation of HER-2/neu-specific CD8+ T cells in PBMCs of breast cancer patients in vitro.
368 15365776 These results gave a good rationale for a phase I/II trial, where the CD80+ HER-2/neu-overexpressing KS variant is actually used as a cellular vaccine in patients with metastatic breast cancer.
369 15365776 As a proof of principle, we present data from two patients where a significant increase of interferon-gamma (IFN-gamma) release was detected when postvaccination PBMCs were stimulated by allogeneic vaccine cells as well as by HLA-A*02-restricted HER-2/neu epitopes.
370 15520206 Previously, we demonstrated that radiation increased Fas (CD95) gene expression in carcinoembryonic antigen (CEA)-expressing murine tumor cells, which consequently enhanced their susceptibility to CEA-specific CTL-mediated killing.
371 15520206 Seventy-two hours postirradiation, changes in surface expression of Fas (CD95), as well as expression of other surface molecules involved in T-cell-mediated immune attack such as intercellular adhesion molecule 1, mucin-1, CEA, and MHC class I, were examined.
372 15520206 Furthermore, five of five irradiated CEA(+)/A2(+) colon tumor cells lines demonstrated significantly enhanced killing by CEA-specific HLA-A2-restricted CD8(+) CTLs compared with nonirradiated counterparts.
373 15520206 Previously, we demonstrated that radiation increased Fas (CD95) gene expression in carcinoembryonic antigen (CEA)-expressing murine tumor cells, which consequently enhanced their susceptibility to CEA-specific CTL-mediated killing.
374 15520206 Seventy-two hours postirradiation, changes in surface expression of Fas (CD95), as well as expression of other surface molecules involved in T-cell-mediated immune attack such as intercellular adhesion molecule 1, mucin-1, CEA, and MHC class I, were examined.
375 15520206 Furthermore, five of five irradiated CEA(+)/A2(+) colon tumor cells lines demonstrated significantly enhanced killing by CEA-specific HLA-A2-restricted CD8(+) CTLs compared with nonirradiated counterparts.
376 15520206 Previously, we demonstrated that radiation increased Fas (CD95) gene expression in carcinoembryonic antigen (CEA)-expressing murine tumor cells, which consequently enhanced their susceptibility to CEA-specific CTL-mediated killing.
377 15520206 Seventy-two hours postirradiation, changes in surface expression of Fas (CD95), as well as expression of other surface molecules involved in T-cell-mediated immune attack such as intercellular adhesion molecule 1, mucin-1, CEA, and MHC class I, were examined.
378 15520206 Furthermore, five of five irradiated CEA(+)/A2(+) colon tumor cells lines demonstrated significantly enhanced killing by CEA-specific HLA-A2-restricted CD8(+) CTLs compared with nonirradiated counterparts.
379 15538731 The favorite target antigens have been those that are frequently expressed by human tumors, such as carcinoembryonic antigen (CEA), ErbB2/neu, and melanoma-associated antigens.
380 15542372 We analyzed MART-1, S-100, MBP, and CD63 for melanoma and p53, MUC1, cyclin B1, HER-2/neu, and CEA for breast cancer.
381 15629278 Panniculitis after vaccination against CEA and MUC1 in a patient with pancreatic cancer.
382 15652670 A DNA vaccine encoding genetic fusions of carcinoembryonic antigen (CEA) and granulocyte/macrophage colony-stimulating factor (GM-CSF).
383 15652670 The anti-tumor immunologic effects of plasmid DNA vaccines encoding human carcinoembryonic antigen (CEA) fused to mouse granulocyte/macrophage colony-stimulating factor (GM-CSF) were examined.
384 15652670 In contrast, a single low-dose immunization with CEA-GMCSF fusion plasmids provided better tumor protection than low-dose CEA plasmid alone and resulted in lower titers of GM-CSF antibodies.
385 15652670 A DNA vaccine encoding genetic fusions of carcinoembryonic antigen (CEA) and granulocyte/macrophage colony-stimulating factor (GM-CSF).
386 15652670 The anti-tumor immunologic effects of plasmid DNA vaccines encoding human carcinoembryonic antigen (CEA) fused to mouse granulocyte/macrophage colony-stimulating factor (GM-CSF) were examined.
387 15652670 In contrast, a single low-dose immunization with CEA-GMCSF fusion plasmids provided better tumor protection than low-dose CEA plasmid alone and resulted in lower titers of GM-CSF antibodies.
388 15652670 A DNA vaccine encoding genetic fusions of carcinoembryonic antigen (CEA) and granulocyte/macrophage colony-stimulating factor (GM-CSF).
389 15652670 The anti-tumor immunologic effects of plasmid DNA vaccines encoding human carcinoembryonic antigen (CEA) fused to mouse granulocyte/macrophage colony-stimulating factor (GM-CSF) were examined.
390 15652670 In contrast, a single low-dose immunization with CEA-GMCSF fusion plasmids provided better tumor protection than low-dose CEA plasmid alone and resulted in lower titers of GM-CSF antibodies.
391 15905566 The correct interaction of a costimulatory molecule such as CD40L with its contrareceptor CD40 expressed on the membrane of professional APCs, provides transmembrane signaling that leads to APC activation.
392 15905566 Therefore, we investigated whether a novel intranasal delivery of immune-reconstituted influenza virosomes (IRIV), assembled with the CD40L gene (CD40L/IRIV), could be used to improve protective immunity and the Ag-specific CTL response against carcinoembryonic Ag (CEA) generated with a novel vaccine constituted of IRIV assembled with the CEA gene (CEA/IRIV).
393 15905566 Our results suggest that CD40L/IRIV was able to augment CEA-specific CTL activity and CEA-specific protective immunity induced by CEA/IRIV most likely through the induction of a CTL response associated with a Th1 phenotype.
394 15905566 In conclusion, we provide evidence that CD40L/IRIV, by acting through the CD40L/CD40 signaling pathway, acts as an immune-adjuvant that could increase the efficacy of a CEA-specific cancer vaccine, which could provide an efficacious new strategy for cancer therapy.
395 15905566 The correct interaction of a costimulatory molecule such as CD40L with its contrareceptor CD40 expressed on the membrane of professional APCs, provides transmembrane signaling that leads to APC activation.
396 15905566 Therefore, we investigated whether a novel intranasal delivery of immune-reconstituted influenza virosomes (IRIV), assembled with the CD40L gene (CD40L/IRIV), could be used to improve protective immunity and the Ag-specific CTL response against carcinoembryonic Ag (CEA) generated with a novel vaccine constituted of IRIV assembled with the CEA gene (CEA/IRIV).
397 15905566 Our results suggest that CD40L/IRIV was able to augment CEA-specific CTL activity and CEA-specific protective immunity induced by CEA/IRIV most likely through the induction of a CTL response associated with a Th1 phenotype.
398 15905566 In conclusion, we provide evidence that CD40L/IRIV, by acting through the CD40L/CD40 signaling pathway, acts as an immune-adjuvant that could increase the efficacy of a CEA-specific cancer vaccine, which could provide an efficacious new strategy for cancer therapy.
399 15905566 The correct interaction of a costimulatory molecule such as CD40L with its contrareceptor CD40 expressed on the membrane of professional APCs, provides transmembrane signaling that leads to APC activation.
400 15905566 Therefore, we investigated whether a novel intranasal delivery of immune-reconstituted influenza virosomes (IRIV), assembled with the CD40L gene (CD40L/IRIV), could be used to improve protective immunity and the Ag-specific CTL response against carcinoembryonic Ag (CEA) generated with a novel vaccine constituted of IRIV assembled with the CEA gene (CEA/IRIV).
401 15905566 Our results suggest that CD40L/IRIV was able to augment CEA-specific CTL activity and CEA-specific protective immunity induced by CEA/IRIV most likely through the induction of a CTL response associated with a Th1 phenotype.
402 15905566 In conclusion, we provide evidence that CD40L/IRIV, by acting through the CD40L/CD40 signaling pathway, acts as an immune-adjuvant that could increase the efficacy of a CEA-specific cancer vaccine, which could provide an efficacious new strategy for cancer therapy.
403 15906358 Injection of plasmid pVIJ/CEA followed by Ad-CEA boost elicited the highest amplitude of both CD4+ and CD8+ T-cell response to the target antigen, measured by both IFNgamma-ELIspot assay and intracellular staining.
404 15906358 Both CD4+ and CD8+ T-cell epitopes were mapped in the C-terminal portion of the protein.
405 15906358 In CEA transgenic mice, only immunization based on repeated injections of pVIJ/CEAopt followed by Ad-CEAopt was able to elicit a CEA-specific CD8+ T-cell response, whereas the wild-type vectors did not break tolerance to this target antigen.
406 15906358 Injection of plasmid pVIJ/CEA followed by Ad-CEA boost elicited the highest amplitude of both CD4+ and CD8+ T-cell response to the target antigen, measured by both IFNgamma-ELIspot assay and intracellular staining.
407 15906358 Both CD4+ and CD8+ T-cell epitopes were mapped in the C-terminal portion of the protein.
408 15906358 In CEA transgenic mice, only immunization based on repeated injections of pVIJ/CEAopt followed by Ad-CEAopt was able to elicit a CEA-specific CD8+ T-cell response, whereas the wild-type vectors did not break tolerance to this target antigen.
409 15930317 Heat shock proteins (HSP) have been revealed to interact with antigen-presenting cells and have potent adjuvant capability to induce antigen-specific CD8+ CTL and Th1 responses.
410 15930317 Our previous work shows how Hsp70-like protein 1 (Hsp70L1), as a new member of the Hsp70 subfamily, acts as potent Th1 adjuvant.
411 15930317 Here, we report the efficient induction of tumor antigen-specific immune response by dendritic cells pulsed with recombinant fusion protein of Hsp70L1 and CEA(576-669) fragment of the carcinoembryonic antigen (CEA) containing CAP-1 (a HLA-A2-restricted CTL epitope).
412 15930317 Fusion protein CEA(576-669)-Hsp70L1 can promote dendritic cell maturation and activate dendritic cells to produce cytokines, such as interleukin-12, interleukin-1beta, and tumor necrosis factor-alpha, and chemokines, such as macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and regulated on activation, normal T expressed and secreted, indicating the adjuvant ability of Hsp70L1 in the fusion protein.
413 15930317 CEA-specific HLA-A2.1-restricted CD8+ CTLs either from patients with CEA+/HLA-A2.1+ colon carcinoma or from splenocytes of immunized HLA-A2.1/Kb transgenic mice can be generated more efficiently after stimulations or immunizations with dendritic cells pulsed by CEA(576-669)-Hsp70L1 than with dendritic cells pulsed by CEA(576-669) alone, resulting in secreting more Th1 cytokine IFN-gamma and killing target cells more potently in an antigen-specific and HLA-A2.1-restricted manner.
414 15930317 Adoptive transfer of splenocytes from transgenic mice immunized with CEA(576-669)-Hsp70L1-pulsed dendritic cells can inhibit tumor growth and prolong survival in nude mice bearing CEA+/HLA-A2.1+ human colon carcinoma more markedly.
415 15930317 Heat shock proteins (HSP) have been revealed to interact with antigen-presenting cells and have potent adjuvant capability to induce antigen-specific CD8+ CTL and Th1 responses.
416 15930317 Our previous work shows how Hsp70-like protein 1 (Hsp70L1), as a new member of the Hsp70 subfamily, acts as potent Th1 adjuvant.
417 15930317 Here, we report the efficient induction of tumor antigen-specific immune response by dendritic cells pulsed with recombinant fusion protein of Hsp70L1 and CEA(576-669) fragment of the carcinoembryonic antigen (CEA) containing CAP-1 (a HLA-A2-restricted CTL epitope).
418 15930317 Fusion protein CEA(576-669)-Hsp70L1 can promote dendritic cell maturation and activate dendritic cells to produce cytokines, such as interleukin-12, interleukin-1beta, and tumor necrosis factor-alpha, and chemokines, such as macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and regulated on activation, normal T expressed and secreted, indicating the adjuvant ability of Hsp70L1 in the fusion protein.
419 15930317 CEA-specific HLA-A2.1-restricted CD8+ CTLs either from patients with CEA+/HLA-A2.1+ colon carcinoma or from splenocytes of immunized HLA-A2.1/Kb transgenic mice can be generated more efficiently after stimulations or immunizations with dendritic cells pulsed by CEA(576-669)-Hsp70L1 than with dendritic cells pulsed by CEA(576-669) alone, resulting in secreting more Th1 cytokine IFN-gamma and killing target cells more potently in an antigen-specific and HLA-A2.1-restricted manner.
420 15930317 Adoptive transfer of splenocytes from transgenic mice immunized with CEA(576-669)-Hsp70L1-pulsed dendritic cells can inhibit tumor growth and prolong survival in nude mice bearing CEA+/HLA-A2.1+ human colon carcinoma more markedly.
421 15930317 Heat shock proteins (HSP) have been revealed to interact with antigen-presenting cells and have potent adjuvant capability to induce antigen-specific CD8+ CTL and Th1 responses.
422 15930317 Our previous work shows how Hsp70-like protein 1 (Hsp70L1), as a new member of the Hsp70 subfamily, acts as potent Th1 adjuvant.
423 15930317 Here, we report the efficient induction of tumor antigen-specific immune response by dendritic cells pulsed with recombinant fusion protein of Hsp70L1 and CEA(576-669) fragment of the carcinoembryonic antigen (CEA) containing CAP-1 (a HLA-A2-restricted CTL epitope).
424 15930317 Fusion protein CEA(576-669)-Hsp70L1 can promote dendritic cell maturation and activate dendritic cells to produce cytokines, such as interleukin-12, interleukin-1beta, and tumor necrosis factor-alpha, and chemokines, such as macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and regulated on activation, normal T expressed and secreted, indicating the adjuvant ability of Hsp70L1 in the fusion protein.
425 15930317 CEA-specific HLA-A2.1-restricted CD8+ CTLs either from patients with CEA+/HLA-A2.1+ colon carcinoma or from splenocytes of immunized HLA-A2.1/Kb transgenic mice can be generated more efficiently after stimulations or immunizations with dendritic cells pulsed by CEA(576-669)-Hsp70L1 than with dendritic cells pulsed by CEA(576-669) alone, resulting in secreting more Th1 cytokine IFN-gamma and killing target cells more potently in an antigen-specific and HLA-A2.1-restricted manner.
426 15930317 Adoptive transfer of splenocytes from transgenic mice immunized with CEA(576-669)-Hsp70L1-pulsed dendritic cells can inhibit tumor growth and prolong survival in nude mice bearing CEA+/HLA-A2.1+ human colon carcinoma more markedly.
427 15930317 Heat shock proteins (HSP) have been revealed to interact with antigen-presenting cells and have potent adjuvant capability to induce antigen-specific CD8+ CTL and Th1 responses.
428 15930317 Our previous work shows how Hsp70-like protein 1 (Hsp70L1), as a new member of the Hsp70 subfamily, acts as potent Th1 adjuvant.
429 15930317 Here, we report the efficient induction of tumor antigen-specific immune response by dendritic cells pulsed with recombinant fusion protein of Hsp70L1 and CEA(576-669) fragment of the carcinoembryonic antigen (CEA) containing CAP-1 (a HLA-A2-restricted CTL epitope).
430 15930317 Fusion protein CEA(576-669)-Hsp70L1 can promote dendritic cell maturation and activate dendritic cells to produce cytokines, such as interleukin-12, interleukin-1beta, and tumor necrosis factor-alpha, and chemokines, such as macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, and regulated on activation, normal T expressed and secreted, indicating the adjuvant ability of Hsp70L1 in the fusion protein.
431 15930317 CEA-specific HLA-A2.1-restricted CD8+ CTLs either from patients with CEA+/HLA-A2.1+ colon carcinoma or from splenocytes of immunized HLA-A2.1/Kb transgenic mice can be generated more efficiently after stimulations or immunizations with dendritic cells pulsed by CEA(576-669)-Hsp70L1 than with dendritic cells pulsed by CEA(576-669) alone, resulting in secreting more Th1 cytokine IFN-gamma and killing target cells more potently in an antigen-specific and HLA-A2.1-restricted manner.
432 15930317 Adoptive transfer of splenocytes from transgenic mice immunized with CEA(576-669)-Hsp70L1-pulsed dendritic cells can inhibit tumor growth and prolong survival in nude mice bearing CEA+/HLA-A2.1+ human colon carcinoma more markedly.
433 16044253 Splenocytes obtained from 3H1-CpG-immunized mice showed an increased proliferative CD4(+) Th1-type T-cell response when stimulated in vitro with 3H1 or CEA and secreted elevated levels of Th1 cytokines (IL-2, IFN-gamma).
434 16044253 This vaccine also induced MHC class I antigen-restricted CD8(+) T-cell responses.
435 16061685 Further, the IFN-gamma enzyme-linked ImmunoSPOT and in vitro 51Cr release assay results showed that HLA-A2-restricted, CEA-specific CTL responses were induced in both mucosal and systemic lymphoid tissues in A2 transgenic mice after oral immunization with PV-CEA.
436 16061685 Finally, we showed that coadministration of papillomavirus pseudoviruses encoding interleukin-2 with PV-CEA enhanced the generation of A2-restricted, CEA-specific CTLs in aged CEA/A2 double transgenic mice, which were more clinically relevant.
437 16061685 Further, the IFN-gamma enzyme-linked ImmunoSPOT and in vitro 51Cr release assay results showed that HLA-A2-restricted, CEA-specific CTL responses were induced in both mucosal and systemic lymphoid tissues in A2 transgenic mice after oral immunization with PV-CEA.
438 16061685 Finally, we showed that coadministration of papillomavirus pseudoviruses encoding interleukin-2 with PV-CEA enhanced the generation of A2-restricted, CEA-specific CTLs in aged CEA/A2 double transgenic mice, which were more clinically relevant.
439 16083220 The main purposes are: 1) To find the correlation of HBV, HCV with CH, LC, HCC. 2) To compare the correlation of Hepatocyte, AFP, CEA (IHC) in malignant cells, which one is the best usage to confirm the diagnosis of HCC in both primary and metastasis. 3) To review the clinicopathology of all these 66 liver samples.
440 16083220 The AFP, CEA show no correlation (p = 0.999, 0.670).
441 16179007 Adenovirus vectors encoding carcinoembryonic antigen (Ad-CEA) or costimulatory molecules CD80, intercellular adhesion molecule-1 (ICAM-1) and leucocyte function-associated antigen-3 (LFA-3) (Ad-STIM) were used to transduce murine bone marrow-derived dendritic cells (BMDC).
442 16179007 Transduction of cells grown in presence of heterologous serum increased the expression of costimulatory molecules, major histocompatibility complex class II, of IL-6 and IL-12.
443 16179007 Nonetheless, CEA-specific CD8+ T-cell response was enhanced upon coinfection of Ad-STIM and Ad-CEA in both mouse strains, although this immune response was not sufficient to protect CEA-tg mice from tumour challenge.
444 16243831 More efficient induction of HLA-A*0201-restricted and carcinoembryonic antigen (CEA)-specific CTL response by immunization with exosomes prepared from heat-stressed CEA-positive tumor cells.
445 16338420 Although a large number of TAAs are available for insertion into viral vectors, this review will discuss the preclinical and clinical development of prostate-specific antigen (PSA) and carcinoembryonic antigen (CEA) poxviral vaccines, as models of the pox viral vaccine approach.
446 16396151 Key advances have included: (1) recognition of the critical role of the antigen-presenting cell and greatly improved understanding of antigen processing and presentation, including the molecular interactions between HLA molecules and antigenic epitopes on the antigen-processing cell and the receptors on T cells, and (2) the roles of costimulatory molecules such as B7.1, ICAM-1, and LFA-3 in the induction and maintenance of an immune response.
447 16396151 By combining various vectors to include MUC-1 and/or CEA plus costimulatory molecules in a prime-and-boost regimen, we are beginning to see signs that this intervention can not only produce changes in immune function but also potentially improve clinical outcomes.
448 16398699 CD8+ T-cell tolerance can be broken by an adenoviral vaccine while CD4+ T-cell tolerance is broken by additional co-administration of a Toll-like receptor ligand.
449 16398699 Immunization of CEA-transgenic mice with an adenoviral vector coding for CEA induced a significant CD8+ T-cell response specific to CEA but failed to induce CEA-specific CD4+ T cells and antibodies.
450 16398699 CD4+-mediated IFN-gamma production was induced in the CEA-transgenic mice only when the genetic immunization was performed in the presence of these adjuvants.
451 16398699 CD8+ T-cell tolerance can be broken by an adenoviral vaccine while CD4+ T-cell tolerance is broken by additional co-administration of a Toll-like receptor ligand.
452 16398699 Immunization of CEA-transgenic mice with an adenoviral vector coding for CEA induced a significant CD8+ T-cell response specific to CEA but failed to induce CEA-specific CD4+ T cells and antibodies.
453 16398699 CD4+-mediated IFN-gamma production was induced in the CEA-transgenic mice only when the genetic immunization was performed in the presence of these adjuvants.
454 16409127 Fusions between CEA and the minimized domain of tetanus toxin fragment C (CEA-DOM) or the Fc portion of IgG1 (CEA-FcIgG) were identified as highly immunogenic and elicited significant CEA-specific antibody and CD8+ T cell responses.
455 16409127 In addition, this protective effect was abrogated if the NK, CD4+, or CD8+ cell population from immunized mice was depleted before tumor challenge.
456 16409127 Passive transfer studies demonstrated that CD4+ and CD8+ T cells and antibodies contributed to the antitumor effect, thus suggesting that a genetic vaccine based on the use of plasmid DNA and adenoviral vectors encoding CEA fused to immunoenhancing sequences augments CEA-specific immune responses and effectively protects from tumor development.
457 16409127 Fusions between CEA and the minimized domain of tetanus toxin fragment C (CEA-DOM) or the Fc portion of IgG1 (CEA-FcIgG) were identified as highly immunogenic and elicited significant CEA-specific antibody and CD8+ T cell responses.
458 16409127 In addition, this protective effect was abrogated if the NK, CD4+, or CD8+ cell population from immunized mice was depleted before tumor challenge.
459 16409127 Passive transfer studies demonstrated that CD4+ and CD8+ T cells and antibodies contributed to the antitumor effect, thus suggesting that a genetic vaccine based on the use of plasmid DNA and adenoviral vectors encoding CEA fused to immunoenhancing sequences augments CEA-specific immune responses and effectively protects from tumor development.
460 16443309 AdVCEA-transduced DC increased antigen-specific T-cell proliferation, augmented the number of IFN-gamma secreting T-cells and induced potent CEA-specific CTL capable of lysing target cells pulsed with CEA peptide, as well as MC38/CEA2 expressing CEA, compared to peptide-pulsed DC.
461 16642271 All breast cancer lines overexpressed the measles virus receptor CD46 and supported robust viral replication, which correlated with CEA production.
462 16830156 However, previous investigations have suggested that G-CSF-mobilized peripheral blood monocytes produce reduced levels of proinflammatory cytokines such as interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha.
463 16830156 In this study, we assessed the functional abilities of DCs generated from G-CSF-mobilized monocytes obtained from 13 patients with CEA-positive advanced solid cancers.
464 16830156 Although G-CSF-mobilized monocytes (G/Mo) less effectively produced Th-1-type cytokines than control monocytes (C/Mo), DCs generated from G/Mo restored the same level of IL-12 production as that seen in DCs generated from C/Mo.
465 17016692 Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells.
466 17016692 We transfected carcinoembryonic antigen (CEA)-expressing tumor cells with a recombinant adenovirus encoding human IL-18 (AdhIL-18) and prepared the exosomes, Exo/IL-18, from IL-18 gene-modified tumor cells.
467 17016692 We found that Exo/IL-18 naturally contain CEA and bioactive IL-18.
468 17016692 Furthermore, Exo/IL-18-pulsed DC are quite potent to induce HLA-A*0201-restricted, CEA-specific CD8(+) CTL from the PBMC of HLA-A*0201 CEA(+) cancer patients in vitro.
469 17016692 Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells.
470 17016692 We transfected carcinoembryonic antigen (CEA)-expressing tumor cells with a recombinant adenovirus encoding human IL-18 (AdhIL-18) and prepared the exosomes, Exo/IL-18, from IL-18 gene-modified tumor cells.
471 17016692 We found that Exo/IL-18 naturally contain CEA and bioactive IL-18.
472 17016692 Furthermore, Exo/IL-18-pulsed DC are quite potent to induce HLA-A*0201-restricted, CEA-specific CD8(+) CTL from the PBMC of HLA-A*0201 CEA(+) cancer patients in vitro.
473 17016692 Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells.
474 17016692 We transfected carcinoembryonic antigen (CEA)-expressing tumor cells with a recombinant adenovirus encoding human IL-18 (AdhIL-18) and prepared the exosomes, Exo/IL-18, from IL-18 gene-modified tumor cells.
475 17016692 We found that Exo/IL-18 naturally contain CEA and bioactive IL-18.
476 17016692 Furthermore, Exo/IL-18-pulsed DC are quite potent to induce HLA-A*0201-restricted, CEA-specific CD8(+) CTL from the PBMC of HLA-A*0201 CEA(+) cancer patients in vitro.
477 17016692 Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells.
478 17016692 We transfected carcinoembryonic antigen (CEA)-expressing tumor cells with a recombinant adenovirus encoding human IL-18 (AdhIL-18) and prepared the exosomes, Exo/IL-18, from IL-18 gene-modified tumor cells.
479 17016692 We found that Exo/IL-18 naturally contain CEA and bioactive IL-18.
480 17016692 Furthermore, Exo/IL-18-pulsed DC are quite potent to induce HLA-A*0201-restricted, CEA-specific CD8(+) CTL from the PBMC of HLA-A*0201 CEA(+) cancer patients in vitro.
481 17053815 CD4+CD25+ regulatory T-cell-inactivation in combination with adenovirus vaccines enhances T-cell responses and protects mice from tumor challenge.
482 17053815 As a transient reduction of immunological tolerance may enable more effective vaccination against self-tumor antigens, we explored this hypothesis in a CEA tolerant animal model with an adenovirus expressing CEA vaccine in conjunction with inactivation of CD4(+)CD25(+) regulatory T cells.
483 17053815 This vaccination modality resulted in increased CEA-specific CD8(+), CD4(+) T cells and antibody response.
484 17053815 CD4+CD25+ regulatory T-cell-inactivation in combination with adenovirus vaccines enhances T-cell responses and protects mice from tumor challenge.
485 17053815 As a transient reduction of immunological tolerance may enable more effective vaccination against self-tumor antigens, we explored this hypothesis in a CEA tolerant animal model with an adenovirus expressing CEA vaccine in conjunction with inactivation of CD4(+)CD25(+) regulatory T cells.
486 17053815 This vaccination modality resulted in increased CEA-specific CD8(+), CD4(+) T cells and antibody response.
487 17096339 This study was designed to determine whether the vaccination of genetically modified dendritic cells (DCs) simultaneously expressing carcinoembryonic antigen (CEA), granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 12 (IL-12) can overcome the peripheral T-cell tolerance to CEA and thereby elicit a therapeutic response in CEA transgenic mice.
488 17096339 The cytotoxic activity of spleen cells against CEA-expressing tumors, MC38-CEA, in the mice immunized with DCs expressing CEA (DC-AxCACEA) was higher than that in those immunized with DCs-AxCALacZ (p < 0.0001), and was augmented by the cotransduction with the GM-CSF/IL-12 gene (p < 0.05).
489 17096339 The vaccination with DC-AxCACEA/GM-CSF/IL-12 could elicit a more potent therapeutic immunity than the vaccination with DC-AxCACEA in subcutaneous tumor models (p < 0.0001), and 4 of 5 mice showed a complete eradication of the subcutaneous tumors in these vaccination groups.
490 17096339 This antitumor activity mostly vanished with the depletion of CD8(+) T cells and NK cells in vivo and was completely abrogated with the depletion of CD4(+) T cells.
491 17096339 This study was designed to determine whether the vaccination of genetically modified dendritic cells (DCs) simultaneously expressing carcinoembryonic antigen (CEA), granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 12 (IL-12) can overcome the peripheral T-cell tolerance to CEA and thereby elicit a therapeutic response in CEA transgenic mice.
492 17096339 The cytotoxic activity of spleen cells against CEA-expressing tumors, MC38-CEA, in the mice immunized with DCs expressing CEA (DC-AxCACEA) was higher than that in those immunized with DCs-AxCALacZ (p < 0.0001), and was augmented by the cotransduction with the GM-CSF/IL-12 gene (p < 0.05).
493 17096339 The vaccination with DC-AxCACEA/GM-CSF/IL-12 could elicit a more potent therapeutic immunity than the vaccination with DC-AxCACEA in subcutaneous tumor models (p < 0.0001), and 4 of 5 mice showed a complete eradication of the subcutaneous tumors in these vaccination groups.
494 17096339 This antitumor activity mostly vanished with the depletion of CD8(+) T cells and NK cells in vivo and was completely abrogated with the depletion of CD4(+) T cells.
495 17133484 We evaluated recombinant MV-Edm expressing carcinoembryonic antigen (CEA) or the human sodium iodide symporter (hNIS) for oncolytic potential in hepatocellular carcinoma (HCC) and efficiency in tracking viruses in vivo by noninvasive monitoring.
496 17133484 MV-Edm expressing CEA or hNIS elicited oncolytic effects in human HCC cell lines in vitro and in vivo, enabling the spread of the virus to be monitored in a noninvasive manner.
497 17133484 We evaluated recombinant MV-Edm expressing carcinoembryonic antigen (CEA) or the human sodium iodide symporter (hNIS) for oncolytic potential in hepatocellular carcinoma (HCC) and efficiency in tracking viruses in vivo by noninvasive monitoring.
498 17133484 MV-Edm expressing CEA or hNIS elicited oncolytic effects in human HCC cell lines in vitro and in vivo, enabling the spread of the virus to be monitored in a noninvasive manner.
499 17182602 Both OK-FCs and Imm-FCs/OK coexpressed the CEA, MUC1, and significantly higher levels of CD86, CD83, and IL-12 than those obtained with Imm-FCs.
500 17182602 Interestingly, OK-FCs were more efficient in stimulating CD4(+) and CD8(+) T cells capable of high levels of IFN-gamma production and cytolysis of autologous tumor or semiallogeneic targets.
501 17182602 The pentameric assay confirmed that CEA- and MUC1-specific CTL was induced simultaneously by OK-FCs at high frequency.
502 17182602 Both OK-FCs and Imm-FCs/OK coexpressed the CEA, MUC1, and significantly higher levels of CD86, CD83, and IL-12 than those obtained with Imm-FCs.
503 17182602 Interestingly, OK-FCs were more efficient in stimulating CD4(+) and CD8(+) T cells capable of high levels of IFN-gamma production and cytolysis of autologous tumor or semiallogeneic targets.
504 17182602 The pentameric assay confirmed that CEA- and MUC1-specific CTL was induced simultaneously by OK-FCs at high frequency.
505 17280474 Enhanced immune responses to an adenovirus CEA vaccine in CD4+CD25+ regulatory T-cell inactivated mice.
506 17318654 Here, we demonstrate a biological synergy between CTLA-4 blockade and active vaccine therapy consisting of recombinant vaccinia and avipox viruses expressing carcinoembryonic antigen (CEA) and three T cell costimulatory molecules to enhance antitumor effects.
507 17363612 Induction of potent and sustained antitumor immunity depends on the efficient activation of CD8(+) and CD4(+) T cells.
508 17363612 Our previous studies suggested that vaccination with an anti-idiotype antibody 3H1, which mimics a specific epitope of carcinoembryonic antigen (CEA), has the potential to break immune tolerance to CEA and induce anti-CEA antibody as well as CEA-specific CD4(+) T-helper responses in colon cancer patients as well as in mice transgenic for human CEA.
509 17363612 The overall immune responses and survival were enhanced in groups of mice immunized with agonist peptide for CEA(691) (YMIGMLVGV)-pulsed dendritic cells or CAP1-6D (YLSGADLNL, agonist peptide for CAP-1)-pulsed dendritic cells.
510 17363612 IFN-gamma ELISPOT and (51)Cr-release assays showed that HLA-A2-restricted, CEA-specific CTL responses were augmented by combined dendritic cell vaccinations.
511 17363612 Induction of potent and sustained antitumor immunity depends on the efficient activation of CD8(+) and CD4(+) T cells.
512 17363612 Our previous studies suggested that vaccination with an anti-idiotype antibody 3H1, which mimics a specific epitope of carcinoembryonic antigen (CEA), has the potential to break immune tolerance to CEA and induce anti-CEA antibody as well as CEA-specific CD4(+) T-helper responses in colon cancer patients as well as in mice transgenic for human CEA.
513 17363612 The overall immune responses and survival were enhanced in groups of mice immunized with agonist peptide for CEA(691) (YMIGMLVGV)-pulsed dendritic cells or CAP1-6D (YLSGADLNL, agonist peptide for CAP-1)-pulsed dendritic cells.
514 17363612 IFN-gamma ELISPOT and (51)Cr-release assays showed that HLA-A2-restricted, CEA-specific CTL responses were augmented by combined dendritic cell vaccinations.
515 17363612 Induction of potent and sustained antitumor immunity depends on the efficient activation of CD8(+) and CD4(+) T cells.
516 17363612 Our previous studies suggested that vaccination with an anti-idiotype antibody 3H1, which mimics a specific epitope of carcinoembryonic antigen (CEA), has the potential to break immune tolerance to CEA and induce anti-CEA antibody as well as CEA-specific CD4(+) T-helper responses in colon cancer patients as well as in mice transgenic for human CEA.
517 17363612 The overall immune responses and survival were enhanced in groups of mice immunized with agonist peptide for CEA(691) (YMIGMLVGV)-pulsed dendritic cells or CAP1-6D (YLSGADLNL, agonist peptide for CAP-1)-pulsed dendritic cells.
518 17363612 IFN-gamma ELISPOT and (51)Cr-release assays showed that HLA-A2-restricted, CEA-specific CTL responses were augmented by combined dendritic cell vaccinations.
519 17373905 PANVAC-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma.
520 17373905 Other strategies that enhance the immune response include the use of granulocyte-macrophage colony-stimulating factor and a prime-boost administration sequence.
521 17440107 Expression of tumor-associated differentiation antigens, MUC1 glycoforms and CEA, in human thymic epithelial cells: implications for self-tolerance and tumor therapy.
522 17440107 We report here promiscuous expression at the protein level of two TAA, MUC1 and CEA, in situ and in purified human mTECs.
523 17440107 Our findings imply that MUC1 and CEA are amenable to central tolerance induction, which might, however, be incomplete in case of tumor cell-restricted MUC1 glycoforms.
524 17440107 Expression of tumor-associated differentiation antigens, MUC1 glycoforms and CEA, in human thymic epithelial cells: implications for self-tolerance and tumor therapy.
525 17440107 We report here promiscuous expression at the protein level of two TAA, MUC1 and CEA, in situ and in purified human mTECs.
526 17440107 Our findings imply that MUC1 and CEA are amenable to central tolerance induction, which might, however, be incomplete in case of tumor cell-restricted MUC1 glycoforms.
527 17440107 Expression of tumor-associated differentiation antigens, MUC1 glycoforms and CEA, in human thymic epithelial cells: implications for self-tolerance and tumor therapy.
528 17440107 We report here promiscuous expression at the protein level of two TAA, MUC1 and CEA, in situ and in purified human mTECs.
529 17440107 Our findings imply that MUC1 and CEA are amenable to central tolerance induction, which might, however, be incomplete in case of tumor cell-restricted MUC1 glycoforms.
530 17447064 The HLA-A*0201-binding CEA(694-702) peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line.
531 17447064 We found that the peptide CEA(694-702) binds weakly to HLA-A*0201 molecules and is ineffective at inducing specific CD8+ T-cell responses in healthy donors.
532 17447064 Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition.
533 17447064 However, the CEA-specific CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition.
534 17447064 The HLA-A*0201-binding CEA(694-702) peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line.
535 17447064 We found that the peptide CEA(694-702) binds weakly to HLA-A*0201 molecules and is ineffective at inducing specific CD8+ T-cell responses in healthy donors.
536 17447064 Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition.
537 17447064 However, the CEA-specific CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition.
538 17447064 The HLA-A*0201-binding CEA(694-702) peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line.
539 17447064 We found that the peptide CEA(694-702) binds weakly to HLA-A*0201 molecules and is ineffective at inducing specific CD8+ T-cell responses in healthy donors.
540 17447064 Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition.
541 17447064 However, the CEA-specific CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition.
542 17447064 The HLA-A*0201-binding CEA(694-702) peptide was recently isolated from acid eluted MHC-I associated peptides from a human colon tumor cell line.
543 17447064 We found that the peptide CEA(694-702) binds weakly to HLA-A*0201 molecules and is ineffective at inducing specific CD8+ T-cell responses in healthy donors.
544 17447064 Tumor cells expressing CEA were recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA expression levels appear to be required for CTL recognition.
545 17447064 However, the CEA-specific CD8+ T-cell clones derived from cancer patients revealed low-functional avidity and impaired tumor-cell recognition.
546 17503041 Moreover, tumor-bearing mice vaccinated with the CEA/TRICOM displayed an antigen cascade, i.e., CD8(+) T cell responses to two other antigens expressed on the tumor and not the vaccine: wild-type p53 and endogenous retroviral antigen gp70.
547 17503041 Mice receiving rF-IL-2 during vaccination demonstrated higher avidity CEA-specific, as well as higher avidity gp70-specific, CD8(+) T cells when compared with mice vaccinated without rF-IL-2.
548 17503041 Moreover, tumor-bearing mice vaccinated with the CEA/TRICOM displayed an antigen cascade, i.e., CD8(+) T cell responses to two other antigens expressed on the tumor and not the vaccine: wild-type p53 and endogenous retroviral antigen gp70.
549 17503041 Mice receiving rF-IL-2 during vaccination demonstrated higher avidity CEA-specific, as well as higher avidity gp70-specific, CD8(+) T cells when compared with mice vaccinated without rF-IL-2.
550 17509725 Autologous DCs were pulsed with apoptotic bodies derived from an allogeneic NSCLC cell line that over-expresses Her2/neu, CEA, WT1, Mage2, and survivin.
551 17564703 Low TCR avidity and lack of tumor cell recognition in CD8(+) T cells primed with the CEA-analogue CAP1-6D peptide.
552 17564703 In the present study, we show that CAP1-6D, a superagonist analogue of a carcinoembriyonic antigen (CEA)-derived HLA-A*0201-restricted epitope widely used in clinical setting, reproducibly promotes the generation of low-affinity CD8(+) T cells lacking the ability to recognized CEA-expressing colorectal carcinoma (CRC) cells.
553 17564703 Short-term T cell cultures, obtained by priming peripheral blood mononuclear cells from HLA-A*0201(+) healthy donors or CRC patients with CAP1-6D, were indeed found to heterogeneously cross-react with saturating concentrations of the native peptide CAP1, but to fail constantly lysing or recognizing through IFN- gamma release CEA(+)CRC cells.
554 17564703 Characterization of anti-CAP1-6D T cell avidity, gained through peptide titration, CD8-dependency assay, and staining with mutated tetramers (D227K/T228A), revealed that anti-CAP1-6D T cells exerted a differential interaction with the two CEA epitopes, i.e., displaying high affinity/CD8-independency toward the APL and low affinity/CD8-dependency toward the native CAP1 peptide.
555 17564703 Low TCR avidity and lack of tumor cell recognition in CD8(+) T cells primed with the CEA-analogue CAP1-6D peptide.
556 17564703 In the present study, we show that CAP1-6D, a superagonist analogue of a carcinoembriyonic antigen (CEA)-derived HLA-A*0201-restricted epitope widely used in clinical setting, reproducibly promotes the generation of low-affinity CD8(+) T cells lacking the ability to recognized CEA-expressing colorectal carcinoma (CRC) cells.
557 17564703 Short-term T cell cultures, obtained by priming peripheral blood mononuclear cells from HLA-A*0201(+) healthy donors or CRC patients with CAP1-6D, were indeed found to heterogeneously cross-react with saturating concentrations of the native peptide CAP1, but to fail constantly lysing or recognizing through IFN- gamma release CEA(+)CRC cells.
558 17564703 Characterization of anti-CAP1-6D T cell avidity, gained through peptide titration, CD8-dependency assay, and staining with mutated tetramers (D227K/T228A), revealed that anti-CAP1-6D T cells exerted a differential interaction with the two CEA epitopes, i.e., displaying high affinity/CD8-independency toward the APL and low affinity/CD8-dependency toward the native CAP1 peptide.
559 17564703 Low TCR avidity and lack of tumor cell recognition in CD8(+) T cells primed with the CEA-analogue CAP1-6D peptide.
560 17564703 In the present study, we show that CAP1-6D, a superagonist analogue of a carcinoembriyonic antigen (CEA)-derived HLA-A*0201-restricted epitope widely used in clinical setting, reproducibly promotes the generation of low-affinity CD8(+) T cells lacking the ability to recognized CEA-expressing colorectal carcinoma (CRC) cells.
561 17564703 Short-term T cell cultures, obtained by priming peripheral blood mononuclear cells from HLA-A*0201(+) healthy donors or CRC patients with CAP1-6D, were indeed found to heterogeneously cross-react with saturating concentrations of the native peptide CAP1, but to fail constantly lysing or recognizing through IFN- gamma release CEA(+)CRC cells.
562 17564703 Characterization of anti-CAP1-6D T cell avidity, gained through peptide titration, CD8-dependency assay, and staining with mutated tetramers (D227K/T228A), revealed that anti-CAP1-6D T cells exerted a differential interaction with the two CEA epitopes, i.e., displaying high affinity/CD8-independency toward the APL and low affinity/CD8-dependency toward the native CAP1 peptide.
563 17564703 Low TCR avidity and lack of tumor cell recognition in CD8(+) T cells primed with the CEA-analogue CAP1-6D peptide.
564 17564703 In the present study, we show that CAP1-6D, a superagonist analogue of a carcinoembriyonic antigen (CEA)-derived HLA-A*0201-restricted epitope widely used in clinical setting, reproducibly promotes the generation of low-affinity CD8(+) T cells lacking the ability to recognized CEA-expressing colorectal carcinoma (CRC) cells.
565 17564703 Short-term T cell cultures, obtained by priming peripheral blood mononuclear cells from HLA-A*0201(+) healthy donors or CRC patients with CAP1-6D, were indeed found to heterogeneously cross-react with saturating concentrations of the native peptide CAP1, but to fail constantly lysing or recognizing through IFN- gamma release CEA(+)CRC cells.
566 17564703 Characterization of anti-CAP1-6D T cell avidity, gained through peptide titration, CD8-dependency assay, and staining with mutated tetramers (D227K/T228A), revealed that anti-CAP1-6D T cells exerted a differential interaction with the two CEA epitopes, i.e., displaying high affinity/CD8-independency toward the APL and low affinity/CD8-dependency toward the native CAP1 peptide.
567 17786327 Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells.
568 17786327 Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs.
569 17786327 In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined.
570 17786327 Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-x(L) expression, leading to the extension of the lifespan of these DCs.
571 17786327 Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-beta1 (TGFbeta-1).
572 17786327 Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFbeta-1 in the regional lymph nodes.
573 17947686 The protective CEA-specific immunity induced by this vaccine consisted of CD4(+) T cell responses with a mixed Th1/Th2 cytokine profile that were accompanied by potent humoral responses, but not by CEA-specific CD8(+) CTL immunity.
574 18055074 The CEA-LTB fusion was shown to elicit a greater CEA-specific antibody and CD8+ T-cell response.
575 18055074 Passive transfer studies demonstrated that CD8+ T cells contribute to the antitumor effect, thus suggesting that a genetic vaccine based on plasmid DNA and adenoviral vectors encoding CEA-LTB augments CEA-specific immune responses and significantly protects from tumor development.
576 18055074 The CEA-LTB fusion was shown to elicit a greater CEA-specific antibody and CD8+ T-cell response.
577 18055074 Passive transfer studies demonstrated that CD8+ T cells contribute to the antitumor effect, thus suggesting that a genetic vaccine based on plasmid DNA and adenoviral vectors encoding CEA-LTB augments CEA-specific immune responses and significantly protects from tumor development.
578 18197807 Preclinical studies have been performed comparing the effects on induction of antigen-specific CD8 and CD4 T-cell responses using recombinant poxvirus vectors containing transgenes for a TAA and costimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM).
579 18197807 We have now completed the first clinical trials with poxvirus vectors containing TRICOM, using the TAAs PSA, CEA, and MUC-1.
580 18202769 DCs adenovirally transduced with the CEA gene were cultured under various conditions with tumor necrosis factor (TNF)-alpha, lipopolysaccharide (LPS), or OK-432.
581 18202769 In all groups (immature DCs, TNF-alpha/DCs, LPS/DCs, OK-432/DCs), CEA-specific CTLs were generated.
582 18202769 OK-432-stimulated DCs (HLA-A24) induced the most potent cytotoxic activity against CEA-expressing targets (A24) but not against controls.
583 18202769 DCs adenovirally transduced with the CEA gene were cultured under various conditions with tumor necrosis factor (TNF)-alpha, lipopolysaccharide (LPS), or OK-432.
584 18202769 In all groups (immature DCs, TNF-alpha/DCs, LPS/DCs, OK-432/DCs), CEA-specific CTLs were generated.
585 18202769 OK-432-stimulated DCs (HLA-A24) induced the most potent cytotoxic activity against CEA-expressing targets (A24) but not against controls.
586 18202769 DCs adenovirally transduced with the CEA gene were cultured under various conditions with tumor necrosis factor (TNF)-alpha, lipopolysaccharide (LPS), or OK-432.
587 18202769 In all groups (immature DCs, TNF-alpha/DCs, LPS/DCs, OK-432/DCs), CEA-specific CTLs were generated.
588 18202769 OK-432-stimulated DCs (HLA-A24) induced the most potent cytotoxic activity against CEA-expressing targets (A24) but not against controls.
589 18209048 One such altered peptide ligand (Cap1-6D) has been derived from an epitope in human carcinoembryonic Ag, CEA(605-613) (Cap1).
590 18209048 We, therefore, examined the T cell repertoires elicited by Cap1-6D and Cap1.
591 18209048 Human CTL lines and clones were generated with either Cap1-6D peptide (6D-CTLs) or Cap1 peptide (Cap1-CTLs).
592 18209048 In contrast, the majority of Cap1-CTLs use different Vbeta1 genes and also had diverse CDR3 lengths. 6D-CTLs produce IFN-gamma in response to Cap1-6D peptide with high avidity, but respond with lower avidity to the native Cap1 peptide when compared with the Cap1-CTLs.
593 18256832 A single dose of Y-90-labeled anti-CEA mAb, in combination with vaccine therapy, resulted in a statistically significant increase in survival in tumor-bearing mice over vaccine or mAb alone; this was shown to be mediated by engagement of the Fas/Fas ligand pathway.
594 18256832 Mice receiving the combination therapy also showed a significant increase in the percentage of viable tumor-infiltrating CEA-specific CD8(+) T cells compared to vaccine alone.
595 18256832 Mice cured of tumors demonstrated an antigen cascade resulting in CD4(+) and CD8(+) T-cell responses not only for CEA, but for p53 and gp70.
596 18256832 A single dose of Y-90-labeled anti-CEA mAb, in combination with vaccine therapy, resulted in a statistically significant increase in survival in tumor-bearing mice over vaccine or mAb alone; this was shown to be mediated by engagement of the Fas/Fas ligand pathway.
597 18256832 Mice receiving the combination therapy also showed a significant increase in the percentage of viable tumor-infiltrating CEA-specific CD8(+) T cells compared to vaccine alone.
598 18256832 Mice cured of tumors demonstrated an antigen cascade resulting in CD4(+) and CD8(+) T-cell responses not only for CEA, but for p53 and gp70.
599 18624349 The B cell vaccine predominantly generated CEA-specific CD4(+) T cells, whereas the DC vaccine generated CD8(+) T cells.
600 18989354 To further enhance the efficacy of DNA-EP, we have evaluated the toll-like receptor7 (TLR7) agonist-2, 9, substituted 8-hydroxyadenosine derivative or SM360320--as an adjuvant to vaccines against HER2/neu and CEA in BALB-neuT and CEA transgenic mice (CEA.Tg), respectively.
601 18989354 SM360320 induced in vivo secretion of interferon alpha (IFNalpha) and exerted a significant antitumor effect in CEA.Tg mice challenged with a syngenic tumor cell line expressing CEA and an additive effect with a CEA vaccine.
602 18989354 These data demonstrate that SM360320 exerts significant antitumor effects and can act in association with DNA-EP for CEA-positive colon cancer and HER2-positive mammary carcinoma.
603 18989354 To further enhance the efficacy of DNA-EP, we have evaluated the toll-like receptor7 (TLR7) agonist-2, 9, substituted 8-hydroxyadenosine derivative or SM360320--as an adjuvant to vaccines against HER2/neu and CEA in BALB-neuT and CEA transgenic mice (CEA.Tg), respectively.
604 18989354 SM360320 induced in vivo secretion of interferon alpha (IFNalpha) and exerted a significant antitumor effect in CEA.Tg mice challenged with a syngenic tumor cell line expressing CEA and an additive effect with a CEA vaccine.
605 18989354 These data demonstrate that SM360320 exerts significant antitumor effects and can act in association with DNA-EP for CEA-positive colon cancer and HER2-positive mammary carcinoma.
606 18989354 To further enhance the efficacy of DNA-EP, we have evaluated the toll-like receptor7 (TLR7) agonist-2, 9, substituted 8-hydroxyadenosine derivative or SM360320--as an adjuvant to vaccines against HER2/neu and CEA in BALB-neuT and CEA transgenic mice (CEA.Tg), respectively.
607 18989354 SM360320 induced in vivo secretion of interferon alpha (IFNalpha) and exerted a significant antitumor effect in CEA.Tg mice challenged with a syngenic tumor cell line expressing CEA and an additive effect with a CEA vaccine.
608 18989354 These data demonstrate that SM360320 exerts significant antitumor effects and can act in association with DNA-EP for CEA-positive colon cancer and HER2-positive mammary carcinoma.
609 19018004 The therapeutic effects were associated with induction of mucosal CEA-specific IgA Ab titers and CD8(+) CTLs.
610 19018004 Mucosal vaccination was also associated with an increase in systemic CEA-specific IgG Ab titers, CD4(+) and CD8(+) T cell responses and resulted in growth inhibition of s.c. implanted CEA-expressing tumors suggesting communication between mucosal and systemic immune compartments.
611 19018004 The therapeutic effects were associated with induction of mucosal CEA-specific IgA Ab titers and CD8(+) CTLs.
612 19018004 Mucosal vaccination was also associated with an increase in systemic CEA-specific IgG Ab titers, CD4(+) and CD8(+) T cell responses and resulted in growth inhibition of s.c. implanted CEA-expressing tumors suggesting communication between mucosal and systemic immune compartments.
613 19066888 The validated primary endpoint assay, a peptide-specific CD8+ IFNgamma ELISPOT, was tested in a pre-trial study and found to be suitable for the detection of low frequency naturally occurring CEA- and prostate-derived tumour-antigen-specific T cells in patients with CEA-expressing malignancies and prostate cancer.
614 19169959 To facilitate in vivo monitoring of viral gene expression and replication, these oncolytic strains have been engineered to either express soluble marker peptides, such as the human carcinoembryonic antigen (CEA; MV-CEA virus), or genes that facilitate imaging and therapy, such as the human thyroidal sodium iodide symporter (NIS) gene (MV-NIS).
615 19212634 FCs of OK432-treated DCs and heat-stressed tumor cells (modified FCs) showed significant up-regulation of tumor-associated CEA and HER-2 antigen, and DC-related HLA-DR and co-stimulatory molecules (CD83 and CD86).
616 19212634 FCs showed significantly higher IFN-gamma and CTL productivity of CD8+ T cells than DCs pulsed with soluble or freeze-thawed tumor cell lysates.
617 19561534 In this study, we developed HHD/carcinoembryonic antigen P(CEA) hybrid mice by breeding transgenic mice homozygous for CEA with HHD.
618 19561534 Owing to the immune tolerance, HHD/CEA mice show a limited immune response and expansion of a different and restricted T-cell receptor repertoire after antigen-specific stimulation.
619 19561534 Most importantly, efficient lysis of human CEA+/HLA-A2.1+ tumor cells was observed and significant protection against HHD/CEA tumor cells was achieved in HHD/CEA-vaccinated mice.
620 19561534 Hence, HHD/CEA provides a relevant model for the evaluation of the potential efficacy of human CEA-based vaccines.
621 19561534 In this study, we developed HHD/carcinoembryonic antigen P(CEA) hybrid mice by breeding transgenic mice homozygous for CEA with HHD.
622 19561534 Owing to the immune tolerance, HHD/CEA mice show a limited immune response and expansion of a different and restricted T-cell receptor repertoire after antigen-specific stimulation.
623 19561534 Most importantly, efficient lysis of human CEA+/HLA-A2.1+ tumor cells was observed and significant protection against HHD/CEA tumor cells was achieved in HHD/CEA-vaccinated mice.
624 19561534 Hence, HHD/CEA provides a relevant model for the evaluation of the potential efficacy of human CEA-based vaccines.
625 19561534 In this study, we developed HHD/carcinoembryonic antigen P(CEA) hybrid mice by breeding transgenic mice homozygous for CEA with HHD.
626 19561534 Owing to the immune tolerance, HHD/CEA mice show a limited immune response and expansion of a different and restricted T-cell receptor repertoire after antigen-specific stimulation.
627 19561534 Most importantly, efficient lysis of human CEA+/HLA-A2.1+ tumor cells was observed and significant protection against HHD/CEA tumor cells was achieved in HHD/CEA-vaccinated mice.
628 19561534 Hence, HHD/CEA provides a relevant model for the evaluation of the potential efficacy of human CEA-based vaccines.
629 19561534 In this study, we developed HHD/carcinoembryonic antigen P(CEA) hybrid mice by breeding transgenic mice homozygous for CEA with HHD.
630 19561534 Owing to the immune tolerance, HHD/CEA mice show a limited immune response and expansion of a different and restricted T-cell receptor repertoire after antigen-specific stimulation.
631 19561534 Most importantly, efficient lysis of human CEA+/HLA-A2.1+ tumor cells was observed and significant protection against HHD/CEA tumor cells was achieved in HHD/CEA-vaccinated mice.
632 19561534 Hence, HHD/CEA provides a relevant model for the evaluation of the potential efficacy of human CEA-based vaccines.
633 19863224 GM-CSF, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-4, IL-8, IL-1b, IL-5, IL-10, IL-12, MIP-1b, IP-10 and Eotaxin were analyzed in a multiplex assay with a Luminex 100 instrument.
634 19863224 CEA and TIMP-1 were analysed on ELISA platforms.
635 19863224 Patients achieving stable disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5.
636 19863224 Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels.
637 19863224 GM-CSF, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-4, IL-8, IL-1b, IL-5, IL-10, IL-12, MIP-1b, IP-10 and Eotaxin were analyzed in a multiplex assay with a Luminex 100 instrument.
638 19863224 CEA and TIMP-1 were analysed on ELISA platforms.
639 19863224 Patients achieving stable disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5.
640 19863224 Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels.
641 19914543 Data of clinical activity have been observed by using vaccines targeting HER-2/neu protein, human telomerase reverse transcriptase, carcinoembryonic antigen (CEA), and carbohydrate antigen given after stem cell rescue.
642 20037300 However, the serum level of CEA elevated since the MUC-1 peptide was used instead of autologous tumor- lysate, even DUPAN-2 did not.
643 20361185 Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA.
644 20361185 The CEA immunogenicity and in vivo anti-tumor effects of repeated immunizations with Ad5 [E1-, E2b-]-CEA compared with those observed with current generation Ad5 [E1-]-CEA were tested in Ad5 pre-immunized mice.
645 20361185 We report that Ad5-immune mice immunized multiple times with Ad5 [E1-, E2b-]-CEA induced CEA-specific CMI responses that were significantly increased over those detected in Ad5-immune mice immunized multiple times with a current generation Ad5 [E1-]-CEA.
646 20361185 Ad5 immune mice bearing CEA-expressing tumors that were treated with Ad5 [E1-, E2b-]-CEA had increased anti-tumor response as compared with Ad5 [E1-]-CEA treated mice.
647 20361185 These results demonstrate that Ad5 [E1-, E2b-]-CEA can induce CMI immune responses which result in tumor growth inhibition despite the presence of pre-existing Ad5 immunity.
648 20361185 Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA.
649 20361185 The CEA immunogenicity and in vivo anti-tumor effects of repeated immunizations with Ad5 [E1-, E2b-]-CEA compared with those observed with current generation Ad5 [E1-]-CEA were tested in Ad5 pre-immunized mice.
650 20361185 We report that Ad5-immune mice immunized multiple times with Ad5 [E1-, E2b-]-CEA induced CEA-specific CMI responses that were significantly increased over those detected in Ad5-immune mice immunized multiple times with a current generation Ad5 [E1-]-CEA.
651 20361185 Ad5 immune mice bearing CEA-expressing tumors that were treated with Ad5 [E1-, E2b-]-CEA had increased anti-tumor response as compared with Ad5 [E1-]-CEA treated mice.
652 20361185 These results demonstrate that Ad5 [E1-, E2b-]-CEA can induce CMI immune responses which result in tumor growth inhibition despite the presence of pre-existing Ad5 immunity.
653 20361185 Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA.
654 20361185 The CEA immunogenicity and in vivo anti-tumor effects of repeated immunizations with Ad5 [E1-, E2b-]-CEA compared with those observed with current generation Ad5 [E1-]-CEA were tested in Ad5 pre-immunized mice.
655 20361185 We report that Ad5-immune mice immunized multiple times with Ad5 [E1-, E2b-]-CEA induced CEA-specific CMI responses that were significantly increased over those detected in Ad5-immune mice immunized multiple times with a current generation Ad5 [E1-]-CEA.
656 20361185 Ad5 immune mice bearing CEA-expressing tumors that were treated with Ad5 [E1-, E2b-]-CEA had increased anti-tumor response as compared with Ad5 [E1-]-CEA treated mice.
657 20361185 These results demonstrate that Ad5 [E1-, E2b-]-CEA can induce CMI immune responses which result in tumor growth inhibition despite the presence of pre-existing Ad5 immunity.
658 20361185 Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA.
659 20361185 The CEA immunogenicity and in vivo anti-tumor effects of repeated immunizations with Ad5 [E1-, E2b-]-CEA compared with those observed with current generation Ad5 [E1-]-CEA were tested in Ad5 pre-immunized mice.
660 20361185 We report that Ad5-immune mice immunized multiple times with Ad5 [E1-, E2b-]-CEA induced CEA-specific CMI responses that were significantly increased over those detected in Ad5-immune mice immunized multiple times with a current generation Ad5 [E1-]-CEA.
661 20361185 Ad5 immune mice bearing CEA-expressing tumors that were treated with Ad5 [E1-, E2b-]-CEA had increased anti-tumor response as compared with Ad5 [E1-]-CEA treated mice.
662 20361185 These results demonstrate that Ad5 [E1-, E2b-]-CEA can induce CMI immune responses which result in tumor growth inhibition despite the presence of pre-existing Ad5 immunity.
663 20361185 Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA.
664 20361185 The CEA immunogenicity and in vivo anti-tumor effects of repeated immunizations with Ad5 [E1-, E2b-]-CEA compared with those observed with current generation Ad5 [E1-]-CEA were tested in Ad5 pre-immunized mice.
665 20361185 We report that Ad5-immune mice immunized multiple times with Ad5 [E1-, E2b-]-CEA induced CEA-specific CMI responses that were significantly increased over those detected in Ad5-immune mice immunized multiple times with a current generation Ad5 [E1-]-CEA.
666 20361185 Ad5 immune mice bearing CEA-expressing tumors that were treated with Ad5 [E1-, E2b-]-CEA had increased anti-tumor response as compared with Ad5 [E1-]-CEA treated mice.
667 20361185 These results demonstrate that Ad5 [E1-, E2b-]-CEA can induce CMI immune responses which result in tumor growth inhibition despite the presence of pre-existing Ad5 immunity.
668 20384858 Interruption of immune regulatory pathways via CTL-associated antigen-4 (CTLA-4) blockade or removal of CD4(+) CD25(+) regulatory T (Treg) cells appears to be a promising strategy for cancer immunotherapy.
669 20384858 In this study, we tested the hypothesis that the combination of CTLA-4 blockade and depletion of Treg cells would improve the potency of dendritic cell (DC)-based vaccine in a clinically relevant mouse model, which is transgenic for both carcinoembryonic antigen (CEA) and HLA-A2 for the treatment of colon carcinoma in a therapeutic setting.
670 20384858 We found that administration of anti-CD25 antibody prior to vaccination or systemic administration of anti-CTLA-4 antibody with the vaccine improved tumour-free survival against CEA-expressing tumours compared with mice immunized with DC-based vaccine alone.
671 20384858 The combined vaccination strategy resulted in increased secretion of IFN-gamma and enhanced HLA-A2-restricted CEA-specific CTL responses.
672 20384858 Interruption of immune regulatory pathways via CTL-associated antigen-4 (CTLA-4) blockade or removal of CD4(+) CD25(+) regulatory T (Treg) cells appears to be a promising strategy for cancer immunotherapy.
673 20384858 In this study, we tested the hypothesis that the combination of CTLA-4 blockade and depletion of Treg cells would improve the potency of dendritic cell (DC)-based vaccine in a clinically relevant mouse model, which is transgenic for both carcinoembryonic antigen (CEA) and HLA-A2 for the treatment of colon carcinoma in a therapeutic setting.
674 20384858 We found that administration of anti-CD25 antibody prior to vaccination or systemic administration of anti-CTLA-4 antibody with the vaccine improved tumour-free survival against CEA-expressing tumours compared with mice immunized with DC-based vaccine alone.
675 20384858 The combined vaccination strategy resulted in increased secretion of IFN-gamma and enhanced HLA-A2-restricted CEA-specific CTL responses.
676 20384858 Interruption of immune regulatory pathways via CTL-associated antigen-4 (CTLA-4) blockade or removal of CD4(+) CD25(+) regulatory T (Treg) cells appears to be a promising strategy for cancer immunotherapy.
677 20384858 In this study, we tested the hypothesis that the combination of CTLA-4 blockade and depletion of Treg cells would improve the potency of dendritic cell (DC)-based vaccine in a clinically relevant mouse model, which is transgenic for both carcinoembryonic antigen (CEA) and HLA-A2 for the treatment of colon carcinoma in a therapeutic setting.
678 20384858 We found that administration of anti-CD25 antibody prior to vaccination or systemic administration of anti-CTLA-4 antibody with the vaccine improved tumour-free survival against CEA-expressing tumours compared with mice immunized with DC-based vaccine alone.
679 20384858 The combined vaccination strategy resulted in increased secretion of IFN-gamma and enhanced HLA-A2-restricted CEA-specific CTL responses.
680 20472099 This vaccination (DCNLGPCEA) elicits mitogen induced and CEA specific T cell proliferation, IFN gamma secretion and induces specific cytotoxic reactions to CEA(+) colon tumor cells.
681 20472099 In support, significant upregulation of CD44 on the surface of lymphocytes from DCNLGPCEA immunized mice was noticed with a substantial reduction in L-selectin (CD62L).
682 20816019 The immunological consequences of the treatment were evaluated with plasma- and serum-levels of inflammatory and non-inflammatory markers (the following 10 cytokines: GM-CSF, INF-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNF-alpha, and in addition the inflammatory chemokines MIP-1beta, Eotaxin and IP-10) and biomarkers CEA and TIMP-1.
683 20816019 These analyses showed that the vaccine induced increasing levels of Th1 cytokines such as GM-CSF, TNF-alpha, IFN-gamma, and IL-2 in patients achieving stable disease.
684 20816019 Patients with progressive disease had increasing levels of CEA and TIMP-1, while patients achieving stable disease maintained relatively stable levels.
685 20816019 The immunological consequences of the treatment were evaluated with plasma- and serum-levels of inflammatory and non-inflammatory markers (the following 10 cytokines: GM-CSF, INF-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNF-alpha, and in addition the inflammatory chemokines MIP-1beta, Eotaxin and IP-10) and biomarkers CEA and TIMP-1.
686 20816019 These analyses showed that the vaccine induced increasing levels of Th1 cytokines such as GM-CSF, TNF-alpha, IFN-gamma, and IL-2 in patients achieving stable disease.
687 20816019 Patients with progressive disease had increasing levels of CEA and TIMP-1, while patients achieving stable disease maintained relatively stable levels.
688 20883737 The combined therapy also increased CEA-specific Th1 and cytotoxic T-cell responses.
689 21189474 Intradermal vaccinations with RNA coding for TAA generate CD8+ and CD4+ immune responses and induce clinical benefit in vaccinated patients.
690 21189474 The aim of this phase I/II nonrandomized trial was to assess feasibility, safety as well as immunological and clinical responses of a mRNA-based vaccination in patients with stage IV renal cell cancer using granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvant.
691 21189474 Intradermal injections of in vitro transcribed naked mRNA, which was generated using plasmids coding for the tumor-associated antigens mucin 1(MUC1), carcinoembryonic (CEA), human epidermal growth factor receptor 2 (Her-2/neu), telomerase, survivin, and melanoma-associated antigen 1 (MAGE-A1) were performed in 30 enrolled patients.
692 21189474 Induction of CD4(+) and CD8(+) T cell responses was shown for several tumor-associated antigens (TAA) using interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and Cr-release assays.
693 21374323 Some tumor antigens are specific for activated cells of certain types, such as carcinoembryonic antigen (CEA) or the IL-2 receptor.
694 21869824 Wild-type and CEA transgenic (Tg) mice were immunized with rAAV-expressing CEA, the TLR9 agonist, oligodinucleotide (ODN)1826 and the TLR7 agonist, imiquimod.
695 21945963 Splenocytes from mice vaccinated with a mixture of TAT-CEA fusion protein and poly(I:C) effectively induced CEA-specific IFN-γ-producing T cells and showed cytotoxic activity specific for MC-38-cea2 tumor cells expressing CEA.
696 22001882 To investigate this possibility, we created adenoviral vectors expressing the extracellular domain (ECD) of two non-mutated TAAs often found in tumors of cancer patients, carcinoembryonic antigen (CEA) and HER2, and coupled them to the C1C2 domain of lactadherin.
697 22068656 A pilot study of MUC-1/CEA/TRICOM poxviral-based vaccine in patients with metastatic breast and ovarian cancer.
698 22110233 Importantly, T-cell responses were positive towards DCs pulsed with several synthetic peptides including Carcinoembryonic antigen (CEA), Melanoma associated antigen (MAGE)1 and MAGE3.
699 22163010 Mannose receptor (MR) engagement by mesothelin GPI anchor polarizes tumor-associated macrophages and is blocked by anti-MR human recombinant antibody.
700 22163010 Many tumor antigens are heavily glycosylated, such as tumoral mucins, and/or attached to tumor cells by mannose residue-containing glycolipids (GPI anchors), as for example mesothelin and the family of carcinoembryonic antigen (CEA).
701 22163010 We found that soluble mesothelin bound to human macrophages and that the binding depended on the presence of GPI anchor and of mannose receptor.
702 22163010 Anti-CDR4-MR scFv #G11 could block mesothelin binding to macrophages and prevent tumor-induced phenotype polarization of CD206(low) macrophages towards TAMs.
703 22163010 Our findings indicate that tumor-released mesothelin is linked to GPI anchor, engages macrophage mannose receptor, and contributes to macrophage polarization towards TAMs.
704 22163010 We propose that compounds able to block tumor antigen GPI anchor/CD206 interactions, such as our novel anti-CRD4-MR scFv, could prevent tumor-induced TAM polarization and have therapeutic potential against ovarian cancer, through polarization control of tumor-infiltrating innate immune cells.
705 22382876 Induction of IgM, IgA and IgE antibodies in colorectal cancer patients vaccinated with a recombinant CEA protein.
706 22488274 We hypothesized that local injection of VRP-expressing interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and antitumor efficacy.
707 22488274 Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)), and VRP-IL-12 was also administered at the same site or at a distant location.
708 23497415 Phase 1 studies of the safety and immunogenicity of electroporated HER2/CEA DNA vaccine followed by adenoviral boost immunization in patients with solid tumors.
709 23624851 Indeed, multiple homologous immunizations with Ad5 [E1-, E2b-]-CEA(6D), encoding the tumor antigen carcinoembryonic antigen (CEA), induced CEA-specific cell-mediated immune (CMI) responses with antitumor activity in mice despite the presence of preexisting or induced Ad5-neutralizing antibody.
710 23624851 In the present phase I/II study, cohorts of patients with advanced colorectal cancer were immunized with escalating doses of Ad5 [E1-, E2b-]-CEA(6D).
711 23624851 Indeed, multiple homologous immunizations with Ad5 [E1-, E2b-]-CEA(6D), encoding the tumor antigen carcinoembryonic antigen (CEA), induced CEA-specific cell-mediated immune (CMI) responses with antitumor activity in mice despite the presence of preexisting or induced Ad5-neutralizing antibody.
712 23624851 In the present phase I/II study, cohorts of patients with advanced colorectal cancer were immunized with escalating doses of Ad5 [E1-, E2b-]-CEA(6D).
713 23657083 A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer.
714 24195644 Genetic cancer vaccines based on in vivo muscle electro-gene-transfer of plasmid DNA (DNA-EGT) and adenoviral vectors represent promising modalities to elicit powerful immune responses against tumor-associated antigens (TAAs) such as carcinoembryonic antigen (CEA) and human epidermal growth factor receptor-2 (HER2)/neu.
715 24195644 We have generated a dual component-dual target genetic cancer vaccine consisting of a DNA moiety containing equal amounts of two plasmids, one encoding the extracellular and transmembrane domains of HER2 (ECD.TM) and the other encoding CEA fused to the B subunit of Escherichia coli heat-labile toxin (LTB), and of an adenoviral subtype 6 dicistronic vector carrying the same two tumor antigens gene constructs.
716 24195644 The CEA/HER2 vaccine was tested in two different CEA/HER2 double-transgenic mouse models and in NOD/scid-DR1 mice engrafted with the human immune system.
717 24195644 The CEA/HER2 vaccine was able to break immune tolerance against both antigens.
718 24195644 In conclusion, the CEA/HER2 genetic vaccine was immunogenic and able to confer significant therapeutic effects.
719 24195644 Genetic cancer vaccines based on in vivo muscle electro-gene-transfer of plasmid DNA (DNA-EGT) and adenoviral vectors represent promising modalities to elicit powerful immune responses against tumor-associated antigens (TAAs) such as carcinoembryonic antigen (CEA) and human epidermal growth factor receptor-2 (HER2)/neu.
720 24195644 We have generated a dual component-dual target genetic cancer vaccine consisting of a DNA moiety containing equal amounts of two plasmids, one encoding the extracellular and transmembrane domains of HER2 (ECD.TM) and the other encoding CEA fused to the B subunit of Escherichia coli heat-labile toxin (LTB), and of an adenoviral subtype 6 dicistronic vector carrying the same two tumor antigens gene constructs.
721 24195644 The CEA/HER2 vaccine was tested in two different CEA/HER2 double-transgenic mouse models and in NOD/scid-DR1 mice engrafted with the human immune system.
722 24195644 The CEA/HER2 vaccine was able to break immune tolerance against both antigens.
723 24195644 In conclusion, the CEA/HER2 genetic vaccine was immunogenic and able to confer significant therapeutic effects.
724 24195644 Genetic cancer vaccines based on in vivo muscle electro-gene-transfer of plasmid DNA (DNA-EGT) and adenoviral vectors represent promising modalities to elicit powerful immune responses against tumor-associated antigens (TAAs) such as carcinoembryonic antigen (CEA) and human epidermal growth factor receptor-2 (HER2)/neu.
725 24195644 We have generated a dual component-dual target genetic cancer vaccine consisting of a DNA moiety containing equal amounts of two plasmids, one encoding the extracellular and transmembrane domains of HER2 (ECD.TM) and the other encoding CEA fused to the B subunit of Escherichia coli heat-labile toxin (LTB), and of an adenoviral subtype 6 dicistronic vector carrying the same two tumor antigens gene constructs.
726 24195644 The CEA/HER2 vaccine was tested in two different CEA/HER2 double-transgenic mouse models and in NOD/scid-DR1 mice engrafted with the human immune system.
727 24195644 The CEA/HER2 vaccine was able to break immune tolerance against both antigens.
728 24195644 In conclusion, the CEA/HER2 genetic vaccine was immunogenic and able to confer significant therapeutic effects.
729 24195644 Genetic cancer vaccines based on in vivo muscle electro-gene-transfer of plasmid DNA (DNA-EGT) and adenoviral vectors represent promising modalities to elicit powerful immune responses against tumor-associated antigens (TAAs) such as carcinoembryonic antigen (CEA) and human epidermal growth factor receptor-2 (HER2)/neu.
730 24195644 We have generated a dual component-dual target genetic cancer vaccine consisting of a DNA moiety containing equal amounts of two plasmids, one encoding the extracellular and transmembrane domains of HER2 (ECD.TM) and the other encoding CEA fused to the B subunit of Escherichia coli heat-labile toxin (LTB), and of an adenoviral subtype 6 dicistronic vector carrying the same two tumor antigens gene constructs.
731 24195644 The CEA/HER2 vaccine was tested in two different CEA/HER2 double-transgenic mouse models and in NOD/scid-DR1 mice engrafted with the human immune system.
732 24195644 The CEA/HER2 vaccine was able to break immune tolerance against both antigens.
733 24195644 In conclusion, the CEA/HER2 genetic vaccine was immunogenic and able to confer significant therapeutic effects.
734 24195644 Genetic cancer vaccines based on in vivo muscle electro-gene-transfer of plasmid DNA (DNA-EGT) and adenoviral vectors represent promising modalities to elicit powerful immune responses against tumor-associated antigens (TAAs) such as carcinoembryonic antigen (CEA) and human epidermal growth factor receptor-2 (HER2)/neu.
735 24195644 We have generated a dual component-dual target genetic cancer vaccine consisting of a DNA moiety containing equal amounts of two plasmids, one encoding the extracellular and transmembrane domains of HER2 (ECD.TM) and the other encoding CEA fused to the B subunit of Escherichia coli heat-labile toxin (LTB), and of an adenoviral subtype 6 dicistronic vector carrying the same two tumor antigens gene constructs.
736 24195644 The CEA/HER2 vaccine was tested in two different CEA/HER2 double-transgenic mouse models and in NOD/scid-DR1 mice engrafted with the human immune system.
737 24195644 The CEA/HER2 vaccine was able to break immune tolerance against both antigens.
738 24195644 In conclusion, the CEA/HER2 genetic vaccine was immunogenic and able to confer significant therapeutic effects.
739 24790791 We generated a number of minigenes containing epitopes from the carcinoembryonic antigen (CEA) model TAA and utilized muscle DNA electro-gene-transfer (DNA-EGT) to vaccinate HLA-A*0201 (HHD) and CEA/HHD double transgenic mice.
740 24790791 Other candidate components comparatively tested included: helper CD4+ T-cell epitopes, flanking regions for optimal epitope processing (including both proteasome-dependent and furin-dependent polypeptide processing mechanisms), and immunoenhancing moieties.
741 24790791 Through a series of comparative studies and iterations we have identified an optimal minigene scaffold comprising the following elements: human tissue plasminogen activator (TPA) signal peptide, T-cell epitopes connected by furin sensitive linkers, and the E.
742 24790791 The selected epitope modified minigenes (EMM) delivered by DNA-EGT were able to break immune tolerance in CEA/HHD mice and induce a strong immune response against all epitopes tested, independently of their relative positions within the scaffold.
743 24790791 We generated a number of minigenes containing epitopes from the carcinoembryonic antigen (CEA) model TAA and utilized muscle DNA electro-gene-transfer (DNA-EGT) to vaccinate HLA-A*0201 (HHD) and CEA/HHD double transgenic mice.
744 24790791 Other candidate components comparatively tested included: helper CD4+ T-cell epitopes, flanking regions for optimal epitope processing (including both proteasome-dependent and furin-dependent polypeptide processing mechanisms), and immunoenhancing moieties.
745 24790791 Through a series of comparative studies and iterations we have identified an optimal minigene scaffold comprising the following elements: human tissue plasminogen activator (TPA) signal peptide, T-cell epitopes connected by furin sensitive linkers, and the E.
746 24790791 The selected epitope modified minigenes (EMM) delivered by DNA-EGT were able to break immune tolerance in CEA/HHD mice and induce a strong immune response against all epitopes tested, independently of their relative positions within the scaffold.
747 24829746 A randomized pilot phase I study of modified carcinoembryonic antigen (CEA) peptide (CAP1-6D)/montanide/GM-CSF-vaccine in patients with pancreatic adenocarcinoma.
748 25449428 In this study, CEA DNA vaccines plus anti-4-1BB Abs treatment was found to increase Ag-specific CTL activity and antitumor protective responses to MC32 cells.
749 25869226 Xenovaccination with rhCEA resulted in the activation of CD4+ T-cell responses in addition to self-reactive CD8+ T-cells, the development of high-titer antibodies against hCEA, and significant antitumor effects upon challenge with hCEA+ tumor cells.
750 25869226 The superior activity of rhCEAopt compared with hCEAopt was confirmed in hCEA/HHD double-transgenic mice, where potent CD8+ T-cell responses against specific human HLA A*0201 hCEA epitopes were detected.
751 25869226 Xenovaccination with rhCEA resulted in the activation of CD4+ T-cell responses in addition to self-reactive CD8+ T-cells, the development of high-titer antibodies against hCEA, and significant antitumor effects upon challenge with hCEA+ tumor cells.
752 25869226 The superior activity of rhCEAopt compared with hCEAopt was confirmed in hCEA/HHD double-transgenic mice, where potent CD8+ T-cell responses against specific human HLA A*0201 hCEA epitopes were detected.
753 25902414 MC32-S2-2 and MC32-S4-2 cells were not susceptible to lysis by CEA-specific CD8+ T cells.
754 25956394 Extended evaluation of a phase 1/2 trial on dosing, safety, immunogenicity, and overall survival after immunizations with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine in late-stage colorectal cancer.
755 25956394 A phase 1/2 clinical trial evaluating dosing, safety, immunogenicity, and overall survival on metastatic colorectal cancer (mCRC) patients after immunotherapy with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine was performed.
756 25956394 Preliminary results revealed that activated CD4+ and CD8+ T cells were detected in a post-immunization sample exhibiting high CMI activity.
757 25956394 Based upon the favorable safety and immunogenicity data obtained, we plan to perform an extensive immunologic and survival analysis on mCRC patients to be enrolled in a randomized/controlled clinical trial that investigates Ad5 [E1-, E2b-]-CEA(6D) as a single agent with booster immunizations.
758 25956394 Extended evaluation of a phase 1/2 trial on dosing, safety, immunogenicity, and overall survival after immunizations with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine in late-stage colorectal cancer.
759 25956394 A phase 1/2 clinical trial evaluating dosing, safety, immunogenicity, and overall survival on metastatic colorectal cancer (mCRC) patients after immunotherapy with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine was performed.
760 25956394 Preliminary results revealed that activated CD4+ and CD8+ T cells were detected in a post-immunization sample exhibiting high CMI activity.
761 25956394 Based upon the favorable safety and immunogenicity data obtained, we plan to perform an extensive immunologic and survival analysis on mCRC patients to be enrolled in a randomized/controlled clinical trial that investigates Ad5 [E1-, E2b-]-CEA(6D) as a single agent with booster immunizations.
762 25956394 Extended evaluation of a phase 1/2 trial on dosing, safety, immunogenicity, and overall survival after immunizations with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine in late-stage colorectal cancer.
763 25956394 A phase 1/2 clinical trial evaluating dosing, safety, immunogenicity, and overall survival on metastatic colorectal cancer (mCRC) patients after immunotherapy with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine was performed.
764 25956394 Preliminary results revealed that activated CD4+ and CD8+ T cells were detected in a post-immunization sample exhibiting high CMI activity.
765 25956394 Based upon the favorable safety and immunogenicity data obtained, we plan to perform an extensive immunologic and survival analysis on mCRC patients to be enrolled in a randomized/controlled clinical trial that investigates Ad5 [E1-, E2b-]-CEA(6D) as a single agent with booster immunizations.
766 26374823 Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors.
767 26374823 Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients.
768 26374823 We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4+ and CD8+ T cells in vaccinated mice.
769 26374823 We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no "antigenic competition" in in vitro studies of human dendritic cells, or in murine vaccination studies.
770 26374823 Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors.
771 26374823 Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients.
772 26374823 We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4+ and CD8+ T cells in vaccinated mice.
773 26374823 We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no "antigenic competition" in in vitro studies of human dendritic cells, or in murine vaccination studies.
774 26374823 Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors.
775 26374823 Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients.
776 26374823 We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4+ and CD8+ T cells in vaccinated mice.
777 26374823 We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no "antigenic competition" in in vitro studies of human dendritic cells, or in murine vaccination studies.