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Gene Information

Gene symbol: WT1

Gene name: Wilms tumor 1

HGNC ID: 12796

Synonyms: WAGR, WIT-2, AWT1

Related Genes

# Gene Symbol Number of hits
1 ABL1 1 hits
2 B3GAT1 1 hits
3 BAGE 1 hits
4 BCL2 1 hits
5 BIRC5 1 hits
6 CD27 1 hits
7 CD34 1 hits
8 CD4 1 hits
9 CD44 1 hits
10 CD8A 1 hits
11 CEACAM5 1 hits
12 CRP 1 hits
13 CSF1 1 hits
14 CSF2 1 hits
15 CTAG1B 1 hits
16 CTLA4 1 hits
17 ELA2 1 hits
18 ERBB2 1 hits
19 FBXL2 1 hits
20 FOS 1 hits
21 GZMB 1 hits
22 HLA-A 1 hits
23 HLA-B 1 hits
24 HLA-DRB1 1 hits
25 HMMR 1 hits
26 HSPA1A 1 hits
27 HTL 1 hits
28 IFNG 1 hits
29 IL13RA2 1 hits
30 IL4 1 hits
31 IL8 1 hits
32 JAK2 1 hits
33 JARID1D 1 hits
34 JUN 1 hits
35 KDR 1 hits
36 KRT31 1 hits
37 LAMP1 1 hits
38 MAGEA2 1 hits
39 MAGED1 1 hits
40 MPO 1 hits
41 MUC1 1 hits
42 MYC 1 hits
43 NPM1 1 hits
44 PPIB 1 hits
45 PRAME 1 hits
46 PRTN3 1 hits
47 SCT 1 hits
48 SPA17 1 hits
49 SPATA2 1 hits
50 TERT 1 hits
51 TMEM37 1 hits
52 TNF 1 hits
53 TNFRSF10A 1 hits
54 TP53 1 hits
55 ZNF224 1 hits

Related Sentences

# PMID Sentence
1 10941827 We recently have reported that Wilms' tumor gene WT1 is highly expressed not only in leukemias but also in various types of solid tumors and that WT1 protein is a novel tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited by immunization with 9-mer WT1 peptides capable of binding to major histocompatibility complex (MHC) class I molecules.
2 10941827 The mice vaccinated with the WT1 plasmid DNA elicited CTLs against the WT1 protein, and the CTLs specifically killed WT1-expressing tumor cells in a MHC class I-restricted manner.
3 10941827 We recently have reported that Wilms' tumor gene WT1 is highly expressed not only in leukemias but also in various types of solid tumors and that WT1 protein is a novel tumor antigen against which cytotoxic T lymphocytes (CTLs) can be elicited by immunization with 9-mer WT1 peptides capable of binding to major histocompatibility complex (MHC) class I molecules.
4 10941827 The mice vaccinated with the WT1 plasmid DNA elicited CTLs against the WT1 protein, and the CTLs specifically killed WT1-expressing tumor cells in a MHC class I-restricted manner.
5 10942395 C57/BL6 (B6) mice were injected with synthetic peptides from the natural sequence of WT1 containing motifs for binding to major histocompatibility (MHC) class II molecules.
6 10942395 Immunization with MHC class I binding peptides induced WT1 peptide-specific cytotoxic T-lymphocyte (CTL) that specifically lysed TRAMP-C and BLKSV40.
7 10942395 C57/BL6 (B6) mice were injected with synthetic peptides from the natural sequence of WT1 containing motifs for binding to major histocompatibility (MHC) class II molecules.
8 10942395 Immunization with MHC class I binding peptides induced WT1 peptide-specific cytotoxic T-lymphocyte (CTL) that specifically lysed TRAMP-C and BLKSV40.
9 12188920 Peripheral blood mononuclear cells (PBMC) from an HLA-A2.1-psitive donor were repeatedly stimulated in vitro with TAP-deficient T2 cells pulsed with each of these two peptides, and CD8-positive cytotoxic T lymphocytes (CTLs) that specifically lyse WT1-expressing, HLA-A2.1-positive tumor cells were induced.
10 12200377 CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia.
11 12200377 Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in vitro and in murine models.
12 12200377 We performed this study to investigate whether WT1- and proteinase 3-specific CD8 T cells spontaneously occur in AML patients.
13 12200377 T cells recognizing HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be detected ex vivo in 5 of 15 HLA-A2-positive AML patients by interferon-gamma (IFN-gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3 additional patients by flow cytometry only.
14 12200377 T cells producing IFN-gamma in response to proteinase 3 were further characterized in one patient by 4-color flow cytometry, identifying them as CD3(+)CD8(+)CD45RA(+) CCR7(-) T cells, resembling cytotoxic effector T cells.
15 12200377 In line with this phenotype, most of the WT1- and proteinase-reactive T cells were granzyme B(+).
16 12200377 These data therefore support the immunogenicity of WT1 and proteinase 3 in acute leukemia patients and the potential usefulness of these antigens for leukemia vaccines.
17 12200377 CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia.
18 12200377 Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in vitro and in murine models.
19 12200377 We performed this study to investigate whether WT1- and proteinase 3-specific CD8 T cells spontaneously occur in AML patients.
20 12200377 T cells recognizing HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be detected ex vivo in 5 of 15 HLA-A2-positive AML patients by interferon-gamma (IFN-gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3 additional patients by flow cytometry only.
21 12200377 T cells producing IFN-gamma in response to proteinase 3 were further characterized in one patient by 4-color flow cytometry, identifying them as CD3(+)CD8(+)CD45RA(+) CCR7(-) T cells, resembling cytotoxic effector T cells.
22 12200377 In line with this phenotype, most of the WT1- and proteinase-reactive T cells were granzyme B(+).
23 12200377 These data therefore support the immunogenicity of WT1 and proteinase 3 in acute leukemia patients and the potential usefulness of these antigens for leukemia vaccines.
24 12200377 CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia.
25 12200377 Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in vitro and in murine models.
26 12200377 We performed this study to investigate whether WT1- and proteinase 3-specific CD8 T cells spontaneously occur in AML patients.
27 12200377 T cells recognizing HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be detected ex vivo in 5 of 15 HLA-A2-positive AML patients by interferon-gamma (IFN-gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3 additional patients by flow cytometry only.
28 12200377 T cells producing IFN-gamma in response to proteinase 3 were further characterized in one patient by 4-color flow cytometry, identifying them as CD3(+)CD8(+)CD45RA(+) CCR7(-) T cells, resembling cytotoxic effector T cells.
29 12200377 In line with this phenotype, most of the WT1- and proteinase-reactive T cells were granzyme B(+).
30 12200377 These data therefore support the immunogenicity of WT1 and proteinase 3 in acute leukemia patients and the potential usefulness of these antigens for leukemia vaccines.
31 12200377 CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia.
32 12200377 Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in vitro and in murine models.
33 12200377 We performed this study to investigate whether WT1- and proteinase 3-specific CD8 T cells spontaneously occur in AML patients.
34 12200377 T cells recognizing HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be detected ex vivo in 5 of 15 HLA-A2-positive AML patients by interferon-gamma (IFN-gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3 additional patients by flow cytometry only.
35 12200377 T cells producing IFN-gamma in response to proteinase 3 were further characterized in one patient by 4-color flow cytometry, identifying them as CD3(+)CD8(+)CD45RA(+) CCR7(-) T cells, resembling cytotoxic effector T cells.
36 12200377 In line with this phenotype, most of the WT1- and proteinase-reactive T cells were granzyme B(+).
37 12200377 These data therefore support the immunogenicity of WT1 and proteinase 3 in acute leukemia patients and the potential usefulness of these antigens for leukemia vaccines.
38 12200377 CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia.
39 12200377 Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in vitro and in murine models.
40 12200377 We performed this study to investigate whether WT1- and proteinase 3-specific CD8 T cells spontaneously occur in AML patients.
41 12200377 T cells recognizing HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be detected ex vivo in 5 of 15 HLA-A2-positive AML patients by interferon-gamma (IFN-gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3 additional patients by flow cytometry only.
42 12200377 T cells producing IFN-gamma in response to proteinase 3 were further characterized in one patient by 4-color flow cytometry, identifying them as CD3(+)CD8(+)CD45RA(+) CCR7(-) T cells, resembling cytotoxic effector T cells.
43 12200377 In line with this phenotype, most of the WT1- and proteinase-reactive T cells were granzyme B(+).
44 12200377 These data therefore support the immunogenicity of WT1 and proteinase 3 in acute leukemia patients and the potential usefulness of these antigens for leukemia vaccines.
45 12200377 CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia.
46 12200377 Wilms tumor gene product WT1 and proteinase 3 are overexpressed antigens in acute myeloid leukemia (AML), against which cytotoxic T lymphocytes can be elicited in vitro and in murine models.
47 12200377 We performed this study to investigate whether WT1- and proteinase 3-specific CD8 T cells spontaneously occur in AML patients.
48 12200377 T cells recognizing HLA-A2.1-binding epitopes from WT1 or proteinase 3 could be detected ex vivo in 5 of 15 HLA-A2-positive AML patients by interferon-gamma (IFN-gamma) ELISPOT assay and flow cytometry for intracellular IFN-gamma and in 3 additional patients by flow cytometry only.
49 12200377 T cells producing IFN-gamma in response to proteinase 3 were further characterized in one patient by 4-color flow cytometry, identifying them as CD3(+)CD8(+)CD45RA(+) CCR7(-) T cells, resembling cytotoxic effector T cells.
50 12200377 In line with this phenotype, most of the WT1- and proteinase-reactive T cells were granzyme B(+).
51 12200377 These data therefore support the immunogenicity of WT1 and proteinase 3 in acute leukemia patients and the potential usefulness of these antigens for leukemia vaccines.
52 12862419 Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia.
53 12862419 DCs must express HLA class I/II molecules and the costimulatory molecules CD40, CD80 and CD86 to effectively activate T cells for the subsequent lysis of leukemic blasts.
54 12862419 The sustained mRNA expression of LAAs such as PRAME, RHAMM or WT-1 proved that the AML-DCs originated from AML blasts.
55 12862419 Compared with AML blasts, the expression of CD40, CD80, CD86 and HLA-DR was upregulated during DC culture to a median of 80-98% on AML-DCs.
56 12862419 Expression of CD40, CD80 and CD83 remained lower on AML-DCs than on HV-DCs.
57 14696097 The following antigens showed high mRNA expression in AML patients: MPP11 was detected in 43/50 (86%), RHAMM in 35/50 (70%), WT1 in 40/60 (67%), PRAME in 32/50 (64%), G250 in 18/35 (51%), hTERT in 7/25 (28%) and BAGE in 8/30 (27%) of AML patients.
58 14696097 Real-time RT-PCR showed a tumor-specific expression of the antigens BAGE, G250 and hTERT, as well as highly tumor-restricted expression for RHAMM, PRAME and WT1.
59 14696097 The following antigens showed high mRNA expression in AML patients: MPP11 was detected in 43/50 (86%), RHAMM in 35/50 (70%), WT1 in 40/60 (67%), PRAME in 32/50 (64%), G250 in 18/35 (51%), hTERT in 7/25 (28%) and BAGE in 8/30 (27%) of AML patients.
60 14696097 Real-time RT-PCR showed a tumor-specific expression of the antigens BAGE, G250 and hTERT, as well as highly tumor-restricted expression for RHAMM, PRAME and WT1.
61 15031530 In phase I clinical trials of WT1 peptide-based cancer immunotherapy, two patients with advanced lung cancer were intradermally injected with 0.3 mg of an HLA-A*2402-restricted, 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant.
62 15365188 Patients were intradermally injected with an HLA-A*2402-restricted, natural, or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant at 0.3, 1.0, or 3.0 mg per body at 2-week intervals, with toxicity and clinical and immunological responses as the principal endpoints.
63 15494301 Vaccines using overexposed self-antigens such as WT1 and PR1 are other attempts to induce a T-cell mediated response against MDS.
64 15944330 Here, we characterized ex vivo responses of CD8 T cells from CML patients to extrajunction bcr-abl peptides and telomerase 540-548 hTert, PR1, and WT1 peptides.
65 15944330 CML-specific CD8 T cells were present in most treated patients and were usually multiepitopic: WT1, hTert, PR1, and bcr74 tetramer(+) cells were detected in 85, 82, 67, and 61% of patients, respectively.
66 15944330 CML-specific tetramer(+) CD8 T cells had a predominantly memory phenotype, an intermediate perforin content, and low intracellular IFN-gamma accumulation in the presence of the relevant peptide.
67 15944330 Here, we characterized ex vivo responses of CD8 T cells from CML patients to extrajunction bcr-abl peptides and telomerase 540-548 hTert, PR1, and WT1 peptides.
68 15944330 CML-specific CD8 T cells were present in most treated patients and were usually multiepitopic: WT1, hTert, PR1, and bcr74 tetramer(+) cells were detected in 85, 82, 67, and 61% of patients, respectively.
69 15944330 CML-specific tetramer(+) CD8 T cells had a predominantly memory phenotype, an intermediate perforin content, and low intracellular IFN-gamma accumulation in the presence of the relevant peptide.
70 16121214 While several leukemia-related antigens have been identified, this review focuses on the Wilms' tumor 1 (WT1) antigen and the proteinase 3 (Pr3) antigen that are overexpressed in leukemic cells and are already being used in the clinical setting.
71 16121214 Examples of spontaneous immune responses against WT1 and Pr3 in leukemia patients are presented and the potential of WT1 and Pr3 for adoptive T-cell immunotherapy of leukemia is discussed.
72 16121214 While several leukemia-related antigens have been identified, this review focuses on the Wilms' tumor 1 (WT1) antigen and the proteinase 3 (Pr3) antigen that are overexpressed in leukemic cells and are already being used in the clinical setting.
73 16121214 Examples of spontaneous immune responses against WT1 and Pr3 in leukemia patients are presented and the potential of WT1 and Pr3 for adoptive T-cell immunotherapy of leukemia is discussed.
74 16220325 Since WT1 encodes MHC class I-restricted peptides recognized by cytotoxic T lymphocytes (CTL), WT1 has been considered as a promising tumor-associated antigen (TAA) for developing anticancer immunotherapy.
75 16220325 Interestingly, the two WT1 HTL epitopes described here are closely situated to known MHC class I-restricted CTL epitopes, raising the possibility of stimulating CTL and HTL responses using a relatively small synthetic peptide vaccine.
76 16220325 Since WT1 encodes MHC class I-restricted peptides recognized by cytotoxic T lymphocytes (CTL), WT1 has been considered as a promising tumor-associated antigen (TAA) for developing anticancer immunotherapy.
77 16220325 Interestingly, the two WT1 HTL epitopes described here are closely situated to known MHC class I-restricted CTL epitopes, raising the possibility of stimulating CTL and HTL responses using a relatively small synthetic peptide vaccine.
78 16533527 Fifty HLA-A*0201 peptides were selected from several target oncoproteins: Wilms' tumor protein (WT1), native and imatinib-mutated bcr-abl p210, JAK2 protein and Ewing's sarcoma fusion protein type 1.
79 16533753 WT1(235), a ninemer peptide derived from Wilms' tumor gene product, is a candidate peptide for the vaccination of HLA-A*0201-positive patients with hematopoietic malignancies.
80 16918359 Human cytotoxic T lymphocytes (CTLs) which could specifically lyse WT1-expressing tumor cells with HLA class I restriction were generated in vitro.
81 16918359 CD8+ WT1-specific CTLs were also detected in peripheral blood or tumor-draining lymph nodes of cancer patients.
82 16918359 Human cytotoxic T lymphocytes (CTLs) which could specifically lyse WT1-expressing tumor cells with HLA class I restriction were generated in vitro.
83 16918359 CD8+ WT1-specific CTLs were also detected in peripheral blood or tumor-draining lymph nodes of cancer patients.
84 16990779 A number of synthetic peptides derived from nonamer sequences of the WT1 protein were designed in which single amino-acid substitutions were introduced at HLA-A0201 major histocompatibility complex (MHC)-binding positions.
85 17145602 Current clinical peptide vaccination trials targeting different epitopes of the Wilms' tumor gene 1 (WT1), the proteinase-3 derived epitope peptide (PR1) and the receptor for hyaluronic acid mediated motility (RHAMM/CD168)-derived epitope R3 are reviewed, and perspectives but also limitations of immunotherapeutic approaches for AML patients are discussed.
86 17414319 Identification and characterization of a WT1 (Wilms Tumor Gene) protein-derived HLA-DRB1*0405-restricted 16-mer helper peptide that promotes the induction and activation of WT1-specific cytotoxic T lymphocytes.
87 17414319 In this study, we identified a WT1 protein-derived 16-mer peptide, WT1(332)(KRYFKLSHLQMHSRKH), which was restricted with HLA-DRB1*0405, one of the most common HLA class II types in Japanese, as a helper epitope that could elicit WT1-specific CD4+ T-cell responses.
88 17414319 We established a WT1(332)-specific CD4+ helper T-cell clone (E04.1), which could respond to both HLA-DRB1*0405-positive, WT1-expressing transformed hematopoietic cells and autologous dendritic cells pulsed with apoptosis-induced WT1-expressing cells, indicating that the WT1(332) was a naturally processed helper epitope.
89 17414319 Stimulation of peripheral blood mononuclear cells with both the CTL epitope (WT1(235)) and the helper epitope (WT1(332)) in the presence of WT1(332)-specific TH1-type CD4+ T cell clone strikingly enhanced the induction and the functional activity of WT1(235)-specific CTLs compared with that of peripheral blood mononuclear cells with the WT1(235) alone.
90 17414319 Identification and characterization of a WT1 (Wilms Tumor Gene) protein-derived HLA-DRB1*0405-restricted 16-mer helper peptide that promotes the induction and activation of WT1-specific cytotoxic T lymphocytes.
91 17414319 In this study, we identified a WT1 protein-derived 16-mer peptide, WT1(332)(KRYFKLSHLQMHSRKH), which was restricted with HLA-DRB1*0405, one of the most common HLA class II types in Japanese, as a helper epitope that could elicit WT1-specific CD4+ T-cell responses.
92 17414319 We established a WT1(332)-specific CD4+ helper T-cell clone (E04.1), which could respond to both HLA-DRB1*0405-positive, WT1-expressing transformed hematopoietic cells and autologous dendritic cells pulsed with apoptosis-induced WT1-expressing cells, indicating that the WT1(332) was a naturally processed helper epitope.
93 17414319 Stimulation of peripheral blood mononuclear cells with both the CTL epitope (WT1(235)) and the helper epitope (WT1(332)) in the presence of WT1(332)-specific TH1-type CD4+ T cell clone strikingly enhanced the induction and the functional activity of WT1(235)-specific CTLs compared with that of peripheral blood mononuclear cells with the WT1(235) alone.
94 17414319 Identification and characterization of a WT1 (Wilms Tumor Gene) protein-derived HLA-DRB1*0405-restricted 16-mer helper peptide that promotes the induction and activation of WT1-specific cytotoxic T lymphocytes.
95 17414319 In this study, we identified a WT1 protein-derived 16-mer peptide, WT1(332)(KRYFKLSHLQMHSRKH), which was restricted with HLA-DRB1*0405, one of the most common HLA class II types in Japanese, as a helper epitope that could elicit WT1-specific CD4+ T-cell responses.
96 17414319 We established a WT1(332)-specific CD4+ helper T-cell clone (E04.1), which could respond to both HLA-DRB1*0405-positive, WT1-expressing transformed hematopoietic cells and autologous dendritic cells pulsed with apoptosis-induced WT1-expressing cells, indicating that the WT1(332) was a naturally processed helper epitope.
97 17414319 Stimulation of peripheral blood mononuclear cells with both the CTL epitope (WT1(235)) and the helper epitope (WT1(332)) in the presence of WT1(332)-specific TH1-type CD4+ T cell clone strikingly enhanced the induction and the functional activity of WT1(235)-specific CTLs compared with that of peripheral blood mononuclear cells with the WT1(235) alone.
98 17414319 Identification and characterization of a WT1 (Wilms Tumor Gene) protein-derived HLA-DRB1*0405-restricted 16-mer helper peptide that promotes the induction and activation of WT1-specific cytotoxic T lymphocytes.
99 17414319 In this study, we identified a WT1 protein-derived 16-mer peptide, WT1(332)(KRYFKLSHLQMHSRKH), which was restricted with HLA-DRB1*0405, one of the most common HLA class II types in Japanese, as a helper epitope that could elicit WT1-specific CD4+ T-cell responses.
100 17414319 We established a WT1(332)-specific CD4+ helper T-cell clone (E04.1), which could respond to both HLA-DRB1*0405-positive, WT1-expressing transformed hematopoietic cells and autologous dendritic cells pulsed with apoptosis-induced WT1-expressing cells, indicating that the WT1(332) was a naturally processed helper epitope.
101 17414319 Stimulation of peripheral blood mononuclear cells with both the CTL epitope (WT1(235)) and the helper epitope (WT1(332)) in the presence of WT1(332)-specific TH1-type CD4+ T cell clone strikingly enhanced the induction and the functional activity of WT1(235)-specific CTLs compared with that of peripheral blood mononuclear cells with the WT1(235) alone.
102 17505014 To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120).
103 17505014 Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8(+) T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05).
104 17505014 To monitor the kinetics of WT1(+) CD8(+) T-cell responses and disease regression after SCT, absolute WT1(+) CD8(+) T-cell numbers and WT1 expression were studied for each time point.
105 17505014 The emergence of WT1(+) CD8(+) T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect.
106 17505014 Loss of WT1(+) CD8(+) T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < .001).
107 17505014 WT1(+) CD8(+) T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma.
108 17505014 Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
109 17505014 To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120).
110 17505014 Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8(+) T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05).
111 17505014 To monitor the kinetics of WT1(+) CD8(+) T-cell responses and disease regression after SCT, absolute WT1(+) CD8(+) T-cell numbers and WT1 expression were studied for each time point.
112 17505014 The emergence of WT1(+) CD8(+) T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect.
113 17505014 Loss of WT1(+) CD8(+) T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < .001).
114 17505014 WT1(+) CD8(+) T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma.
115 17505014 Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
116 17505014 To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120).
117 17505014 Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8(+) T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05).
118 17505014 To monitor the kinetics of WT1(+) CD8(+) T-cell responses and disease regression after SCT, absolute WT1(+) CD8(+) T-cell numbers and WT1 expression were studied for each time point.
119 17505014 The emergence of WT1(+) CD8(+) T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect.
120 17505014 Loss of WT1(+) CD8(+) T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < .001).
121 17505014 WT1(+) CD8(+) T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma.
122 17505014 Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
123 17505014 To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120).
124 17505014 Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8(+) T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05).
125 17505014 To monitor the kinetics of WT1(+) CD8(+) T-cell responses and disease regression after SCT, absolute WT1(+) CD8(+) T-cell numbers and WT1 expression were studied for each time point.
126 17505014 The emergence of WT1(+) CD8(+) T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect.
127 17505014 Loss of WT1(+) CD8(+) T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < .001).
128 17505014 WT1(+) CD8(+) T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma.
129 17505014 Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
130 17505014 To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120).
131 17505014 Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8(+) T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05).
132 17505014 To monitor the kinetics of WT1(+) CD8(+) T-cell responses and disease regression after SCT, absolute WT1(+) CD8(+) T-cell numbers and WT1 expression were studied for each time point.
133 17505014 The emergence of WT1(+) CD8(+) T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect.
134 17505014 Loss of WT1(+) CD8(+) T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < .001).
135 17505014 WT1(+) CD8(+) T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma.
136 17505014 Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
137 17505014 To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120).
138 17505014 Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8(+) T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05).
139 17505014 To monitor the kinetics of WT1(+) CD8(+) T-cell responses and disease regression after SCT, absolute WT1(+) CD8(+) T-cell numbers and WT1 expression were studied for each time point.
140 17505014 The emergence of WT1(+) CD8(+) T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect.
141 17505014 Loss of WT1(+) CD8(+) T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < .001).
142 17505014 WT1(+) CD8(+) T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma.
143 17505014 Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
144 17505014 To determine whether the leukemia-associated Wilms tumor antigen (WT1) contributes to a graft-versus-leukemia (GVL) effect after allogeneic stem-cell transplantation (SCT) for acute lymphoblastic leukemia (ALL), we studied CD8(+) T-cell responses to WT1 in 10 human lymphocyte antigen (HLA)-A*0201-positive ALL patients during the early phase of immune recovery after SCT (days 30-120).
145 17505014 Using WT1/HLA-A*0201 tetramers and intracellular interferon-gamma (IFN-gamma) staining, WT1(+) CD8(+) T-cell responses after SCT were found only in patients with detectable WT1 expression before SCT (5 of 7 vs. 0 of 3; P < .05).
146 17505014 To monitor the kinetics of WT1(+) CD8(+) T-cell responses and disease regression after SCT, absolute WT1(+) CD8(+) T-cell numbers and WT1 expression were studied for each time point.
147 17505014 The emergence of WT1(+) CD8(+) T cells was associated with a decrease in WT1 expression, suggesting a WT1-driven GVL effect.
148 17505014 Loss of WT1(+) CD8(+) T-cell responses was associated with reappearance of WT1 transcripts, consistent with a molecular relapse (P < .001).
149 17505014 WT1(+) CD8(+) T cells had a predominantly effector-memory phenotype (CD45RO(+) CD27(-)CD57(+)) and produced IFN-gamma.
150 17505014 Our results support the immunogenicity of WT1 after SCT for ALL and highlight the potential for WT1 vaccines to boost GVL after SCT for ALL.
151 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.
152 17524167 Preferentially expressed in CD34+ haematopoietic progenitors and down-regulated in more-differentiated cells, the WT1 transcription factor has been implicated in regulation of apoptosis, proliferation and differentiation.
153 17524167 Putative target genes, such as BCL2, MYC, A1 and cyclin E, may cooperate with WT1 to modulate cell growth.
154 17524167 In vitro killing of tumour cells by WT1-specific CD8+ cytotoxic T lymphocytes facilitated design of Phase I vaccine trials that showed clinical regression of WT1-positive tumours.
155 17524167 Preferentially expressed in CD34+ haematopoietic progenitors and down-regulated in more-differentiated cells, the WT1 transcription factor has been implicated in regulation of apoptosis, proliferation and differentiation.
156 17524167 Putative target genes, such as BCL2, MYC, A1 and cyclin E, may cooperate with WT1 to modulate cell growth.
157 17524167 In vitro killing of tumour cells by WT1-specific CD8+ cytotoxic T lymphocytes facilitated design of Phase I vaccine trials that showed clinical regression of WT1-positive tumours.
158 17524167 Preferentially expressed in CD34+ haematopoietic progenitors and down-regulated in more-differentiated cells, the WT1 transcription factor has been implicated in regulation of apoptosis, proliferation and differentiation.
159 17524167 Putative target genes, such as BCL2, MYC, A1 and cyclin E, may cooperate with WT1 to modulate cell growth.
160 17524167 In vitro killing of tumour cells by WT1-specific CD8+ cytotoxic T lymphocytes facilitated design of Phase I vaccine trials that showed clinical regression of WT1-positive tumours.
161 17562620 In a phase I clinical trial of biweekly vaccination with HLA-A*2402-restricted WT1 peptide for these malignancies, 2 patients with MDS developed severe leukocytopenia in association with a reduction in leukemic blast cells and levels of WT1 messenger RNA (mRNA) after only a single vaccination with 0.3 mg of WT1 peptide.
162 17579261 In this study, we treated three patients with renal cell carcinoma with an anchor modified, HLA-A*2402 binding WT1 peptide which was emulsified in Freund's incomplete adjuvant.
163 17619750 Human cytotoxic T lymphocytes (CTLs), which could specifically lyse WT1-expressing tumor cells with HLA class I restriction, were generated in vitro.
164 17619750 CD8+ WT1-specific CTLs were also detected in peripheral blood or tumor-draining lymph nodes of cancer patients.
165 17619750 Human cytotoxic T lymphocytes (CTLs), which could specifically lyse WT1-expressing tumor cells with HLA class I restriction, were generated in vitro.
166 17619750 CD8+ WT1-specific CTLs were also detected in peripheral blood or tumor-draining lymph nodes of cancer patients.
167 17875804 Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies.
168 17875804 We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1.
169 17875804 Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor.
170 17875804 Using peptide/HLA-A 0201 tetramers and intracellular interferon-gamma staining, CD8(+) T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination.
171 17875804 To monitor the kinetics of vaccine-induced CD8(+) T-cell responses and disease regression after vaccination, absolute PR1 and WT1(+)CD8(+) T-cell numbers and WT1 expression were studied weekly after vaccination.
172 17875804 After vaccination, the emergence of PR1 or WT1(+)CD8(+) T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect.
173 17875804 This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic.
174 17875804 Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies.
175 17875804 We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1.
176 17875804 Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor.
177 17875804 Using peptide/HLA-A 0201 tetramers and intracellular interferon-gamma staining, CD8(+) T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination.
178 17875804 To monitor the kinetics of vaccine-induced CD8(+) T-cell responses and disease regression after vaccination, absolute PR1 and WT1(+)CD8(+) T-cell numbers and WT1 expression were studied weekly after vaccination.
179 17875804 After vaccination, the emergence of PR1 or WT1(+)CD8(+) T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect.
180 17875804 This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic.
181 17875804 Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies.
182 17875804 We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1.
183 17875804 Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor.
184 17875804 Using peptide/HLA-A 0201 tetramers and intracellular interferon-gamma staining, CD8(+) T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination.
185 17875804 To monitor the kinetics of vaccine-induced CD8(+) T-cell responses and disease regression after vaccination, absolute PR1 and WT1(+)CD8(+) T-cell numbers and WT1 expression were studied weekly after vaccination.
186 17875804 After vaccination, the emergence of PR1 or WT1(+)CD8(+) T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect.
187 17875804 This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic.
188 17875804 Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies.
189 17875804 We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1.
190 17875804 Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor.
191 17875804 Using peptide/HLA-A 0201 tetramers and intracellular interferon-gamma staining, CD8(+) T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination.
192 17875804 To monitor the kinetics of vaccine-induced CD8(+) T-cell responses and disease regression after vaccination, absolute PR1 and WT1(+)CD8(+) T-cell numbers and WT1 expression were studied weekly after vaccination.
193 17875804 After vaccination, the emergence of PR1 or WT1(+)CD8(+) T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect.
194 17875804 This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic.
195 17875804 Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies.
196 17875804 We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1.
197 17875804 Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor.
198 17875804 Using peptide/HLA-A 0201 tetramers and intracellular interferon-gamma staining, CD8(+) T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination.
199 17875804 To monitor the kinetics of vaccine-induced CD8(+) T-cell responses and disease regression after vaccination, absolute PR1 and WT1(+)CD8(+) T-cell numbers and WT1 expression were studied weekly after vaccination.
200 17875804 After vaccination, the emergence of PR1 or WT1(+)CD8(+) T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect.
201 17875804 This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic.
202 17875804 Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies.
203 17875804 We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1.
204 17875804 Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor.
205 17875804 Using peptide/HLA-A 0201 tetramers and intracellular interferon-gamma staining, CD8(+) T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination.
206 17875804 To monitor the kinetics of vaccine-induced CD8(+) T-cell responses and disease regression after vaccination, absolute PR1 and WT1(+)CD8(+) T-cell numbers and WT1 expression were studied weekly after vaccination.
207 17875804 After vaccination, the emergence of PR1 or WT1(+)CD8(+) T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect.
208 17875804 This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic.
209 17875804 Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies.
210 17875804 We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1.
211 17875804 Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor.
212 17875804 Using peptide/HLA-A 0201 tetramers and intracellular interferon-gamma staining, CD8(+) T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination.
213 17875804 To monitor the kinetics of vaccine-induced CD8(+) T-cell responses and disease regression after vaccination, absolute PR1 and WT1(+)CD8(+) T-cell numbers and WT1 expression were studied weekly after vaccination.
214 17875804 After vaccination, the emergence of PR1 or WT1(+)CD8(+) T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect.
215 17875804 This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic.
216 18192109 The patient received weekly intradermal injections of an HLA-A*2402-restricted 9-mer WT1 peptide emulsified with Montanide ISA 51 adjuvant for 12 weeks and achieved a minimal response according to European Group for Blood and Marrow Transplantation criteria without experiencing systemic adverse effects.
217 18192109 As for immunologic parameters, the frequency of WT1 tetramer-positive cells among CD8+ T-cells, which was higher than in healthy donors, temporarily decreased at weeks 4 and 8 but increased at week 12, whereas the frequency of WT1 peptide-responding CD107a/b+ cells among WT1 tetramer-positive T-cells increased from 27.0% to 38.6% after the vaccination.
218 18192109 The patient received weekly intradermal injections of an HLA-A*2402-restricted 9-mer WT1 peptide emulsified with Montanide ISA 51 adjuvant for 12 weeks and achieved a minimal response according to European Group for Blood and Marrow Transplantation criteria without experiencing systemic adverse effects.
219 18192109 As for immunologic parameters, the frequency of WT1 tetramer-positive cells among CD8+ T-cells, which was higher than in healthy donors, temporarily decreased at weeks 4 and 8 but increased at week 12, whereas the frequency of WT1 peptide-responding CD107a/b+ cells among WT1 tetramer-positive T-cells increased from 27.0% to 38.6% after the vaccination.
220 18502835 We evaluated WT1 as an immunotherapeutic target using our proven DNA fusion vaccine design, p.DOM-peptide, encoding a minimal tumor-derived major histocompatibility complex (MHC) class I-binding epitope downstream of a foreign sequence of tetanus toxin.
221 18548092 To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them with minor histocompatibility antigens (mHAgs) HA1 and SMCY.
222 18548092 Furthermore, WT1 was consistently overexpressed in advanced phase (AdP) CML in all CD34+ subpopulations, and mature progenitors of chronic phase (CP) CML compared to healthy individuals.
223 18548092 Surface expression of WT1 protein in the most primitive hematopoietic stem cells in AdP-CML suggest that they could be targets for WT1 peptide-based vaccines, which in combination with PRAME, could additionally improve targeting differentiated progeny, and benefit patients responding suboptimally to tyrosine kinase inhibitors, or enhance GVL effects in SCT patients.
224 18548092 To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them with minor histocompatibility antigens (mHAgs) HA1 and SMCY.
225 18548092 Furthermore, WT1 was consistently overexpressed in advanced phase (AdP) CML in all CD34+ subpopulations, and mature progenitors of chronic phase (CP) CML compared to healthy individuals.
226 18548092 Surface expression of WT1 protein in the most primitive hematopoietic stem cells in AdP-CML suggest that they could be targets for WT1 peptide-based vaccines, which in combination with PRAME, could additionally improve targeting differentiated progeny, and benefit patients responding suboptimally to tyrosine kinase inhibitors, or enhance GVL effects in SCT patients.
227 18548092 To assess the potential of LAA-peptide vaccines in eliminating leukemia in CML patients, we measured WT1, PR3, ELA2 and PRAME expression in CD34+ progenitor subpopulations in CML patients and compared them with minor histocompatibility antigens (mHAgs) HA1 and SMCY.
228 18548092 Furthermore, WT1 was consistently overexpressed in advanced phase (AdP) CML in all CD34+ subpopulations, and mature progenitors of chronic phase (CP) CML compared to healthy individuals.
229 18548092 Surface expression of WT1 protein in the most primitive hematopoietic stem cells in AdP-CML suggest that they could be targets for WT1 peptide-based vaccines, which in combination with PRAME, could additionally improve targeting differentiated progeny, and benefit patients responding suboptimally to tyrosine kinase inhibitors, or enhance GVL effects in SCT patients.
230 18676860 Importantly, they recognized HLA-DRB1*04-matched fresh leukemic cells expressing the WT1 antigen.
231 18676860 These clones exerted a T helper 2 cytokine profile, had a CD4(+)CD25(+)Foxp3(+)GITR(+)CD127(-) T(reg) phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell contact.
232 18676860 Furthermore, priming of T cells with the WT1-126 HLA-A0201-restricted peptide in the presence of T(regs) strongly inhibited the induction of anti-WT1-126 CD8(+) CTL responses as evidenced by both very low cytotoxic activity and IFN-gamma production.
233 18676860 Moreover, these T(reg) clones specifically produced granzyme B and selectively induced apoptosis in WT1-84-pulsed autologous antigen-presenting cells but not in apoptotic-resistant DR4-matched leukemic cells.
234 18676860 Importantly, we have also detected anti-WT1-84 interleukin-5(+)/granzyme B(+)/Foxp3(+) CD4(+) T(regs) in five of eight HLA-DR4(+) acute myeloid leukemia patients.
235 18676860 Importantly, they recognized HLA-DRB1*04-matched fresh leukemic cells expressing the WT1 antigen.
236 18676860 These clones exerted a T helper 2 cytokine profile, had a CD4(+)CD25(+)Foxp3(+)GITR(+)CD127(-) T(reg) phenotype, and significantly inhibited the proliferative activity of allogeneic T cells independently of cell contact.
237 18676860 Furthermore, priming of T cells with the WT1-126 HLA-A0201-restricted peptide in the presence of T(regs) strongly inhibited the induction of anti-WT1-126 CD8(+) CTL responses as evidenced by both very low cytotoxic activity and IFN-gamma production.
238 18676860 Moreover, these T(reg) clones specifically produced granzyme B and selectively induced apoptosis in WT1-84-pulsed autologous antigen-presenting cells but not in apoptotic-resistant DR4-matched leukemic cells.
239 18676860 Importantly, we have also detected anti-WT1-84 interleukin-5(+)/granzyme B(+)/Foxp3(+) CD4(+) T(regs) in five of eight HLA-DR4(+) acute myeloid leukemia patients.
240 19075652 Based on the analysis of anchor residues that were important for the interaction between peptides and HLA class I molecules, WT1 cytotoxic T lymphocyte (CTL) epitopes with the restriction of HLA-A 0201 and HLA-A 2402 were identified, and clinical trials of WT1 peptide vaccination for cancer patients with these HLA class I types were started.
241 19079589 Thirteen WT1 peptides sequences were synthesized with chemically modified amino acids (via fluorination and photo-reactive group additions) at MHC and T cell receptor binding positions.
242 19197722 Enhancement of lytic activity of leukemic cells by CD8+ cytotoxic T lymphocytes generated against a WT1 peptide analogue.
243 19860194 These include fusion gene products such as BCR-ABL and ETV6-AML1, proteinase 3, WT1, human telomerase reverse transcriptase, cyclophilin B, and PRAME.
244 20400682 Immune responses were evaluated by delayed-type hypersensitivity, CD4+ T-cell proliferation, CD3+ T-cell interferon-gamma release, and WT1 peptide tetramer staining.
245 20400682 Three patients who were HLA-A0201-positive showed significant increase in interferon-gamma-secreting cells and frequency of WT1 tetramer-positive CD8+ T cells.
246 20400682 Immune responses were evaluated by delayed-type hypersensitivity, CD4+ T-cell proliferation, CD3+ T-cell interferon-gamma release, and WT1 peptide tetramer staining.
247 20400682 Three patients who were HLA-A0201-positive showed significant increase in interferon-gamma-secreting cells and frequency of WT1 tetramer-positive CD8+ T cells.
248 20582983 WT1 vaccine was administered to HLA-A*2402-positive patients with WT1-overexpressing residual tumor despite prior conventional treatment.
249 20619457 Structures of native and affinity-enhanced WT1 epitopes bound to HLA-A*0201: implications for WT1-based cancer therapeutics.
250 20619457 Here we determined the structures of the class I MHC molecule HLA-A*0201 bound to the native 126-134 epitope of the WT1 peptide and a recently described variant (R1Y) with improved MHC binding.
251 20619457 Stability measurements revealed how the R1Y substitution enhances MHC binding affinity, and together with the structures suggest a strategy for engineering WT1 variants with improved MHC binding that retain the structural features of the native peptide/MHC complex.
252 20619457 Structures of native and affinity-enhanced WT1 epitopes bound to HLA-A*0201: implications for WT1-based cancer therapeutics.
253 20619457 Here we determined the structures of the class I MHC molecule HLA-A*0201 bound to the native 126-134 epitope of the WT1 peptide and a recently described variant (R1Y) with improved MHC binding.
254 20619457 Stability measurements revealed how the R1Y substitution enhances MHC binding affinity, and together with the structures suggest a strategy for engineering WT1 variants with improved MHC binding that retain the structural features of the native peptide/MHC complex.
255 20619457 Structures of native and affinity-enhanced WT1 epitopes bound to HLA-A*0201: implications for WT1-based cancer therapeutics.
256 20619457 Here we determined the structures of the class I MHC molecule HLA-A*0201 bound to the native 126-134 epitope of the WT1 peptide and a recently described variant (R1Y) with improved MHC binding.
257 20619457 Stability measurements revealed how the R1Y substitution enhances MHC binding affinity, and together with the structures suggest a strategy for engineering WT1 variants with improved MHC binding that retain the structural features of the native peptide/MHC complex.
258 20631300 Clinical responses were correlated with vaccine-associated increases in WT1-specific CD8+ T cell frequencies, as detected by peptide/HLA-A*0201 tetramer staining, and elevated levels of activated natural killer cells postvaccination.
259 20631300 Furthermore, vaccinated patients showed increased levels of WT1-specific IFN-gamma-producing CD8+ T cells and features of general immune activation.
260 20631300 Clinical responses were correlated with vaccine-associated increases in WT1-specific CD8+ T cell frequencies, as detected by peptide/HLA-A*0201 tetramer staining, and elevated levels of activated natural killer cells postvaccination.
261 20631300 Furthermore, vaccinated patients showed increased levels of WT1-specific IFN-gamma-producing CD8+ T cells and features of general immune activation.
262 20885926 Expression of tumor antigens p53, SP17, survivin, WT1, and NY-ESO-1 was observed in 120 (48.0%), 173 (68.9%), 208 (90.0%), 129 (56.3%), and 27 (11.0%) of 270 tumor specimens, respectively.
263 20963411 Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909.
264 20963411 T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials.
265 20963411 To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated.
266 20963411 Neither pre-existing nor naive WT1-/Pr3-/MUC1-specific CD8+ T cells expanded in vivo by vaccination.
267 20963411 An increase in PADRE-specific CD4+ T helper cells was observed after vaccination but these appeared unable to produce IL2, and CD4+ T cells with a regulatory phenotype increased.
268 20963411 Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909.
269 20963411 T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials.
270 20963411 To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated.
271 20963411 Neither pre-existing nor naive WT1-/Pr3-/MUC1-specific CD8+ T cells expanded in vivo by vaccination.
272 20963411 An increase in PADRE-specific CD4+ T helper cells was observed after vaccination but these appeared unable to produce IL2, and CD4+ T cells with a regulatory phenotype increased.
273 20963411 Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909.
274 20963411 T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials.
275 20963411 To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated.
276 20963411 Neither pre-existing nor naive WT1-/Pr3-/MUC1-specific CD8+ T cells expanded in vivo by vaccination.
277 20963411 An increase in PADRE-specific CD4+ T helper cells was observed after vaccination but these appeared unable to produce IL2, and CD4+ T cells with a regulatory phenotype increased.
278 20963411 Pitfalls of vaccinations with WT1-, Proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909.
279 20963411 T cells with specificity for antigens derived from Wilms Tumor gene (WT1), Proteinase3 (Pr3), and mucin1 (MUC1) have been demonstrated to lyse acute myeloid leukemia (AML) blasts and multiple-myeloma (MM) cells, and strategies to enhance or induce such tumor-specific T cells by vaccination are currently being explored in multiple clinical trials.
280 20963411 To test safety and immunogenicity of a vaccine composed of WT1-, Pr3-, and MUC1-derived Class I-restricted peptides and the pan HLA-DR T helper cell epitope (PADRE) or MUC1-helper epitopes in combination with CpG7909 and MontanideISA51, four patients with AML and five with MM were repetitively vaccinated.
281 20963411 Neither pre-existing nor naive WT1-/Pr3-/MUC1-specific CD8+ T cells expanded in vivo by vaccination.
282 20963411 An increase in PADRE-specific CD4+ T helper cells was observed after vaccination but these appeared unable to produce IL2, and CD4+ T cells with a regulatory phenotype increased.
283 21134985 Repeated PR1 and WT1 peptide vaccination in Montanide-adjuvant fails to induce sustained high-avidity, epitope-specific CD8+ T cells in myeloid malignancies.
284 21447831 Thymocytes expressing a WT1-specific T-cell receptor derived from high avidity human CD8 T cells were positively selected into the single-positive CD8 population.
285 21447831 In the periphery, T cells specific for the WT1 antigen differentiated into CD44-high memory phenotype cells, whereas T cells specific for a non-self-viral antigen retained a CD44(low) naive phenotype.
286 21447831 Thymocytes expressing a WT1-specific T-cell receptor derived from high avidity human CD8 T cells were positively selected into the single-positive CD8 population.
287 21447831 In the periphery, T cells specific for the WT1 antigen differentiated into CD44-high memory phenotype cells, whereas T cells specific for a non-self-viral antigen retained a CD44(low) naive phenotype.
288 21518514 [Construction of fusion gene vaccine of WT1 multi-epitope fused with stimulating epitope of mycobacterium tuberculosis heat shock protein 70 and its expression and immunogenicity].
289 21518514 This study was purposed to construct a fusion DNA vaccine containing WT1 multi-epitope and stimulating epitope of mycobacterium tuberculosis heat shock protein 70 and to detect its expression and immunogenicity.
290 21518514 [Construction of fusion gene vaccine of WT1 multi-epitope fused with stimulating epitope of mycobacterium tuberculosis heat shock protein 70 and its expression and immunogenicity].
291 21518514 This study was purposed to construct a fusion DNA vaccine containing WT1 multi-epitope and stimulating epitope of mycobacterium tuberculosis heat shock protein 70 and to detect its expression and immunogenicity.
292 21556630 Meq has an interesting structure, resembling a chimera between Jun/Fos oncoproteins and WT-1 tumor suppressor protein.
293 21654520 WT1 overexpression, present in 56.3% of EOC, was associated with infiltration of Tregs [odds ratio (OR), 2.7; 95% confidence interval (95% CI), 1.6-4.7; P<0.001] and up-regulation of MHC class II (OR, 2.2; 95% CI, 1.2-4.1; P=0.014).
294 21654520 As WT1 overexpressing EOC is associated with CTL and Treg infiltration next to MHC class II up-regulation, future clinical trials should evaluate the combination of therapeutic WT1 vaccines with strategies depleting Tregs and/or up-regulating MHC class I, in an attempt to enhance clinical efficacy in EOC patients.
295 21654520 WT1 overexpression, present in 56.3% of EOC, was associated with infiltration of Tregs [odds ratio (OR), 2.7; 95% confidence interval (95% CI), 1.6-4.7; P<0.001] and up-regulation of MHC class II (OR, 2.2; 95% CI, 1.2-4.1; P=0.014).
296 21654520 As WT1 overexpressing EOC is associated with CTL and Treg infiltration next to MHC class II up-regulation, future clinical trials should evaluate the combination of therapeutic WT1 vaccines with strategies depleting Tregs and/or up-regulating MHC class I, in an attempt to enhance clinical efficacy in EOC patients.
297 21821799 Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity.
298 21821799 T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection.
299 21821799 In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity.
300 21821799 In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides.
301 21821799 In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance.
302 21821799 Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity.
303 21821799 T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection.
304 21821799 In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity.
305 21821799 In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides.
306 21821799 In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance.
307 21821799 Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity.
308 21821799 T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection.
309 21821799 In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity.
310 21821799 In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides.
311 21821799 In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance.
312 21821799 Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity.
313 21821799 T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection.
314 21821799 In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity.
315 21821799 In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides.
316 21821799 In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance.
317 21821799 Allogeneic HLA-A*02-restricted WT1-specific T cells from mismatched donors are highly reactive but show off-target promiscuity.
318 21821799 T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection.
319 21821799 In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity.
320 21821799 In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides.
321 21821799 In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance.
322 21868578 Donor immunization with WT1 peptide augments antileukemic activity after MHC-matched bone marrow transplantation.
323 21868578 WT1 peptide vaccinations of healthy donor mice induced CD8(+) T cells that were specifically reactive to WT1-expressing FBL3 leukemia cells.
324 21868578 The transfer of total CD8(+) T cells from immunized donors was more effective than the transfer of WT1-tetramer(+)CD8(+) T cells and both required CD4(+) T-cell help for maximal antitumor activity.
325 21868578 These findings show that WT1 peptide vaccination of donor mice can dramatically enhance GvT activity after MHC-matched allogeneic BMT.
326 21868578 Donor immunization with WT1 peptide augments antileukemic activity after MHC-matched bone marrow transplantation.
327 21868578 WT1 peptide vaccinations of healthy donor mice induced CD8(+) T cells that were specifically reactive to WT1-expressing FBL3 leukemia cells.
328 21868578 The transfer of total CD8(+) T cells from immunized donors was more effective than the transfer of WT1-tetramer(+)CD8(+) T cells and both required CD4(+) T-cell help for maximal antitumor activity.
329 21868578 These findings show that WT1 peptide vaccination of donor mice can dramatically enhance GvT activity after MHC-matched allogeneic BMT.
330 21868578 Donor immunization with WT1 peptide augments antileukemic activity after MHC-matched bone marrow transplantation.
331 21868578 WT1 peptide vaccinations of healthy donor mice induced CD8(+) T cells that were specifically reactive to WT1-expressing FBL3 leukemia cells.
332 21868578 The transfer of total CD8(+) T cells from immunized donors was more effective than the transfer of WT1-tetramer(+)CD8(+) T cells and both required CD4(+) T-cell help for maximal antitumor activity.
333 21868578 These findings show that WT1 peptide vaccination of donor mice can dramatically enhance GvT activity after MHC-matched allogeneic BMT.
334 21868578 Donor immunization with WT1 peptide augments antileukemic activity after MHC-matched bone marrow transplantation.
335 21868578 WT1 peptide vaccinations of healthy donor mice induced CD8(+) T cells that were specifically reactive to WT1-expressing FBL3 leukemia cells.
336 21868578 The transfer of total CD8(+) T cells from immunized donors was more effective than the transfer of WT1-tetramer(+)CD8(+) T cells and both required CD4(+) T-cell help for maximal antitumor activity.
337 21868578 These findings show that WT1 peptide vaccination of donor mice can dramatically enhance GvT activity after MHC-matched allogeneic BMT.
338 21902290 In myeloid leukaemias, clinical trials of vaccination with peptides derived from a number of leukaemia antigens, including WT1, PR1, RHAMM and BCR-ABL, have shown evidence of immunogenicity, but limited data are available on the clinical efficacy of this approach.
339 22160049 Vaccines can be classified as those against defined antigens such as minor histocompatibility antigens (mHags) or leukemia-associated antigens (PR1, WT1, and BCR-ABL) and those that have broad "antileukemic" activity such as engineered irradiated leukemia cells or leukemia-derived dendritic cells (DCs).
340 22169315 This review focuses on the late results of clinical trails of peptide vaccination protocols targeting WT1, RHAMM, BCR-ABL, PR1 in hematological malignancies and the development of specific immune responses to PRAME and Survivin peptides.
341 22641661 Phase I trial of Wilms' Tumor 1 (WT1) peptide vaccine with GM-CSF or CpG in patients with solid malignancy.
342 23179498 Our group's initial peptide-based glioma vaccine targeting EphA2, IL-13Rα2, and Survivin, which are overexpressed in pediatric gliomas, has shown promise in its initial phase of testing.
343 23179498 We therefore investigated whether EphA2, IL-13Rα2, Survivin, and, additionally, Wilms' Tumor 1 (WT1), are overexpressed in pediatric ependymomas to determine if a similar immunotherapy approach could be applicable.
344 23179498 Immunohistochemistry was performed using antibodies specific for EphA2, IL-13Rα2, Survivin, and WT1 on paraffin-embedded specimens from 19 pediatric and 13 adult ependymomas.
345 23179498 In the 19 pediatric cases, 18 (95 %) demonstrated positive staining for EphA2, 16 (84 %) for IL-13Rα2, 18 (95 %) for Survivin, and only 7 (37 %) for WT1.
346 23179498 Our group's initial peptide-based glioma vaccine targeting EphA2, IL-13Rα2, and Survivin, which are overexpressed in pediatric gliomas, has shown promise in its initial phase of testing.
347 23179498 We therefore investigated whether EphA2, IL-13Rα2, Survivin, and, additionally, Wilms' Tumor 1 (WT1), are overexpressed in pediatric ependymomas to determine if a similar immunotherapy approach could be applicable.
348 23179498 Immunohistochemistry was performed using antibodies specific for EphA2, IL-13Rα2, Survivin, and WT1 on paraffin-embedded specimens from 19 pediatric and 13 adult ependymomas.
349 23179498 In the 19 pediatric cases, 18 (95 %) demonstrated positive staining for EphA2, 16 (84 %) for IL-13Rα2, 18 (95 %) for Survivin, and only 7 (37 %) for WT1.
350 23179498 Our group's initial peptide-based glioma vaccine targeting EphA2, IL-13Rα2, and Survivin, which are overexpressed in pediatric gliomas, has shown promise in its initial phase of testing.
351 23179498 We therefore investigated whether EphA2, IL-13Rα2, Survivin, and, additionally, Wilms' Tumor 1 (WT1), are overexpressed in pediatric ependymomas to determine if a similar immunotherapy approach could be applicable.
352 23179498 Immunohistochemistry was performed using antibodies specific for EphA2, IL-13Rα2, Survivin, and WT1 on paraffin-embedded specimens from 19 pediatric and 13 adult ependymomas.
353 23179498 In the 19 pediatric cases, 18 (95 %) demonstrated positive staining for EphA2, 16 (84 %) for IL-13Rα2, 18 (95 %) for Survivin, and only 7 (37 %) for WT1.
354 23225417 We have been successfully performing WT1 vaccination with a 9-mer modified WT1(235) peptide, which has one amino acid substitution (M→Y) at position 2 of 9-mer natural WT1(235) peptide (235-243 a.a.), for close to 700 HLA-A*24:02-positive patients with leukemia or solid tumors.
355 23225417 In this study, we established a modified WT1(235) peptide-specific CTL clone, we isolated T-cell receptor (TCR) genes from it and transduced the TCR genes into CD8(+) T-cells.
356 23225417 The TCR-transduced CD8(+) T-cells produced interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα) in response to stimulation not only with the modified WT1(235) peptide but also with the natural WT1(235) peptide and lysed modified or natural WT1(235) peptide-pulsed target cells and endogenously WT1-expressing leukemia cells in a HLA-A*24:02-restriction manner.
357 23225417 We have been successfully performing WT1 vaccination with a 9-mer modified WT1(235) peptide, which has one amino acid substitution (M→Y) at position 2 of 9-mer natural WT1(235) peptide (235-243 a.a.), for close to 700 HLA-A*24:02-positive patients with leukemia or solid tumors.
358 23225417 In this study, we established a modified WT1(235) peptide-specific CTL clone, we isolated T-cell receptor (TCR) genes from it and transduced the TCR genes into CD8(+) T-cells.
359 23225417 The TCR-transduced CD8(+) T-cells produced interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα) in response to stimulation not only with the modified WT1(235) peptide but also with the natural WT1(235) peptide and lysed modified or natural WT1(235) peptide-pulsed target cells and endogenously WT1-expressing leukemia cells in a HLA-A*24:02-restriction manner.
360 23225417 We have been successfully performing WT1 vaccination with a 9-mer modified WT1(235) peptide, which has one amino acid substitution (M→Y) at position 2 of 9-mer natural WT1(235) peptide (235-243 a.a.), for close to 700 HLA-A*24:02-positive patients with leukemia or solid tumors.
361 23225417 In this study, we established a modified WT1(235) peptide-specific CTL clone, we isolated T-cell receptor (TCR) genes from it and transduced the TCR genes into CD8(+) T-cells.
362 23225417 The TCR-transduced CD8(+) T-cells produced interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα) in response to stimulation not only with the modified WT1(235) peptide but also with the natural WT1(235) peptide and lysed modified or natural WT1(235) peptide-pulsed target cells and endogenously WT1-expressing leukemia cells in a HLA-A*24:02-restriction manner.
363 23267892 [Prediction of WT1/MUC1 peptide dendritic cell therapy responders by quantification of ex vivo induced mRNA in whole blood].
364 23267892 To challenge this classic problem, we quantified 17 different leukocyte function-associated mRNAs( IFN-γ,TNFSF1, TNFSF2, TNFSF5, IL-10, TGF β,CTLA4, PD1, FOXP3, GMCSF, VEGF, IL-8, CCL8, CXCL3, and IL-2) in whole blood after ex vivo stimulation with 7 different agents(PHA, HAG, zymosan, IFN-γ,rIL-2, aTCR, and picibanil) to activate various subsets of leukocytes.
365 23267892 The clinical outcomes for WT1 peptide-and/or MUC1 peptide-pulsed dendritic cell therapy for advanced cancer (n=26) were CR+PR, 4 cases; SD, 9 cases; and PD, 13 cases.
366 23267892 [Prediction of WT1/MUC1 peptide dendritic cell therapy responders by quantification of ex vivo induced mRNA in whole blood].
367 23267892 To challenge this classic problem, we quantified 17 different leukocyte function-associated mRNAs( IFN-γ,TNFSF1, TNFSF2, TNFSF5, IL-10, TGF β,CTLA4, PD1, FOXP3, GMCSF, VEGF, IL-8, CCL8, CXCL3, and IL-2) in whole blood after ex vivo stimulation with 7 different agents(PHA, HAG, zymosan, IFN-γ,rIL-2, aTCR, and picibanil) to activate various subsets of leukocytes.
368 23267892 The clinical outcomes for WT1 peptide-and/or MUC1 peptide-pulsed dendritic cell therapy for advanced cancer (n=26) were CR+PR, 4 cases; SD, 9 cases; and PD, 13 cases.
369 23428979 Establishment of a stable T lymphoma cell line transduced with HLA-A*24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring.
370 23428979 A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes.
371 23428979 This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02.
372 23428979 This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs.
373 23428979 Establishment of a stable T lymphoma cell line transduced with HLA-A*24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring.
374 23428979 A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes.
375 23428979 This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02.
376 23428979 This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs.
377 23428979 Establishment of a stable T lymphoma cell line transduced with HLA-A*24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring.
378 23428979 A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes.
379 23428979 This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02.
380 23428979 This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs.
381 23428979 Establishment of a stable T lymphoma cell line transduced with HLA-A*24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring.
382 23428979 A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes.
383 23428979 This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02.
384 23428979 This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs.
385 23480492 Ex vivo frequencies of these T cells measured from unfractionated samples by the CD137 activation marker assay were high in many patients (some > 1% CD8+).
386 23480492 Using standard in vitro techniques we discovered that they were cytotoxic to WT1 peptide library-loaded T2 cells and WT1 antigen-primed autologous Epstein-Barr virus-transformed B cell lines (EBV-LCLs) and expressed interferon gamma (IFN-γ).
387 24422723 In six patients, WT1-specific CTL responses were detected using enzyme-linked immunosorbent spot assays and pWT126/HLA-A*0201 tetramer staining, after ex vivo stimulation with the relevant WT1 peptides.
388 24422723 However, re-stimulation of these WT1-specific T cells failed to elicit secondary expansion in all four patients tested, suggesting that the WT1-specific CD8(+) T cells generated following vaccination may be functionally impaired.
389 24422723 In six patients, WT1-specific CTL responses were detected using enzyme-linked immunosorbent spot assays and pWT126/HLA-A*0201 tetramer staining, after ex vivo stimulation with the relevant WT1 peptides.
390 24422723 However, re-stimulation of these WT1-specific T cells failed to elicit secondary expansion in all four patients tested, suggesting that the WT1-specific CD8(+) T cells generated following vaccination may be functionally impaired.
391 24509173 Patients received HLA-A*24:02-restricted, modified 9-mer WT1 peptide (3 mg/body) emulsified with Montanide ISA51 adjuvant (WT1 vaccine) intradermally biweekly and gemcitabine (1000 mg/m) on days 1, 8, and 15 of a 28-day cycle.
392 24633336 P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma.
393 24633336 All TAAs were frequently expressed in pancreatic adenocarcinoma cells, except for adenocarcinoma antigens recognized by T cells 1, melanoma-associated antigen (MAGE)-A1, and MAGE-A3.
394 24633336 Among the epitopes recognized by CTLs in more than two patients in the ELISPOT assay, 6 epitopes derived from 5 TAAs, namely, MAGE-A3, p53, human telomerase reverse transcriptase (hTERT), Wilms tumor (WT)-1, and vascular endothelial growth factor receptor (VEGFR)2, could induce specific CTLs that showed cytotoxicity against pancreatic cancer cell lines.
395 24633336 P53, hTERT, WT-1, and VEGFR2 were shown to be attractive targets for immunotherapy in patients with pancreatic adenocarcinoma, and the induction of TAA-specific CTLs may improve the prognosis of these patients.
396 24633336 P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma.
397 24633336 All TAAs were frequently expressed in pancreatic adenocarcinoma cells, except for adenocarcinoma antigens recognized by T cells 1, melanoma-associated antigen (MAGE)-A1, and MAGE-A3.
398 24633336 Among the epitopes recognized by CTLs in more than two patients in the ELISPOT assay, 6 epitopes derived from 5 TAAs, namely, MAGE-A3, p53, human telomerase reverse transcriptase (hTERT), Wilms tumor (WT)-1, and vascular endothelial growth factor receptor (VEGFR)2, could induce specific CTLs that showed cytotoxicity against pancreatic cancer cell lines.
399 24633336 P53, hTERT, WT-1, and VEGFR2 were shown to be attractive targets for immunotherapy in patients with pancreatic adenocarcinoma, and the induction of TAA-specific CTLs may improve the prognosis of these patients.
400 24649223 Peripheral blood mononuclear cells obtained by leukapheresis were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, OK-432 and prostaglandin E2 to generate DCs, which were pulsed with autologous tumor lysates or tumor-specific peptides, such as WT1.
401 25092142 NPM1, MAGED1, PRTN3, MPO, WT1), but found 80% of them to be also represented in healthy control samples.
402 25205401 A hydrophilic Trojan peptide containing most of the zinc finger-2 domain of WT1 was synthesized and shown to inhibit SK-MEL-28 melanoma growth in vitro.
403 25243629 The extensively validated WT1/c-ABL ratio was used to normalize increases in WT1 transcript levels.
404 25243629 The WT1/c-ABL transcript ratio of 50 or above yielded 100% specificity and 75% sensitivity reliably predicting future relapse with an observed average of 29.4 days (s.d.=19.8) and a calculated average of 63 days (s.d.=29.3) lead time before morphologic confirmation.
405 25243629 The extensively validated WT1/c-ABL ratio was used to normalize increases in WT1 transcript levels.
406 25243629 The WT1/c-ABL transcript ratio of 50 or above yielded 100% specificity and 75% sensitivity reliably predicting future relapse with an observed average of 29.4 days (s.d.=19.8) and a calculated average of 63 days (s.d.=29.3) lead time before morphologic confirmation.
407 25335717 [Efficacy of WT1 peptide-/MUC-1 peptide-pulsed dendritic cell therapy in 313 patients with a wide range of cancers].
408 25335717 We assessed the efficacy of Wilms' tumor protein-1(WT1)peptide and/or mucin 1(MUC-1)peptide-pulsed dendritic cell(DC)therapy for a wide range of advanced cancers.This retrospective study included 313 patients with advanced cancer who were vaccinated ≥5 times in our clinic between May 2009 and October 2013.T he clinical response was evaluated.This treatment was approved by the ethics panel of our institution.A total of 313 patients were injected an average of 6.0 times with DCs(2.4×10 / 7 cells/injection).Overall, 292 of the 313(93%)patients obtained clinical benefit according to the Response Evaluation Criteria in Solid Tumors(RECIST), version 1.1.
409 25335717 [Efficacy of WT1 peptide-/MUC-1 peptide-pulsed dendritic cell therapy in 313 patients with a wide range of cancers].
410 25335717 We assessed the efficacy of Wilms' tumor protein-1(WT1)peptide and/or mucin 1(MUC-1)peptide-pulsed dendritic cell(DC)therapy for a wide range of advanced cancers.This retrospective study included 313 patients with advanced cancer who were vaccinated ≥5 times in our clinic between May 2009 and October 2013.T he clinical response was evaluated.This treatment was approved by the ethics panel of our institution.A total of 313 patients were injected an average of 6.0 times with DCs(2.4×10 / 7 cells/injection).Overall, 292 of the 313(93%)patients obtained clinical benefit according to the Response Evaluation Criteria in Solid Tumors(RECIST), version 1.1.
411 25526950 Endoscopy was used to administer intratumoral injections of dendritic cells (DCs) targeting synthesized peptides of Wilms tumor 1 (WT1) and mucin 1, cell-surface associated (MUC1).
412 25526950 An immunohistochemical analysis of the tumor samples indicated positivity for WT1 and MUC1.
413 25526950 Endoscopy was used to administer intratumoral injections of dendritic cells (DCs) targeting synthesized peptides of Wilms tumor 1 (WT1) and mucin 1, cell-surface associated (MUC1).
414 25526950 An immunohistochemical analysis of the tumor samples indicated positivity for WT1 and MUC1.
415 25614082 Ten HLA-A*2402 patients were treated with WT1 peptide-pulsed DC vaccination (1 × 10(7) cells) on days 8 and 22 and gemcitabine (1000 mg/m(2) ) on days 1, 8 and 15.
416 25614082 Patients with liver metastases and high levels of inflammatory markers such as C-reactive protein and interleukin-8 (IL-8) showed poor survival even though a WT1-specific immune response was induced in them.
417 25614082 Ten HLA-A*2402 patients were treated with WT1 peptide-pulsed DC vaccination (1 × 10(7) cells) on days 8 and 22 and gemcitabine (1000 mg/m(2) ) on days 1, 8 and 15.
418 25614082 Patients with liver metastases and high levels of inflammatory markers such as C-reactive protein and interleukin-8 (IL-8) showed poor survival even though a WT1-specific immune response was induced in them.
419 25802083 Individuals with WT1-positive acute myeloid leukemia (AML) in first (CR1) or second (CR2) remission or with higher-risk myelodysplastic syndrome (MDS) following at least 1 prior line of therapy were vaccinated with a mixture of peptides derived from the WT1 protein, with sargramostim injections before vaccination to amplify immunogenicity.
420 26104661 Antileukemia multifunctionality of CD4(+) T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer.
421 26104661 To develop gene-modified T-cell-based antileukemia adoptive immunotherapy, concomitant administration of CD4(+) and CD8(+) T cells that have been gene modified using identical HLA class I-restricted leukemia antigen-specific T-cell receptor (TCR) gene transfer has not yet been fully investigated.
422 26104661 Here, using CD4(+) and CD8(+) T cells that had been gene modified with a retroviral vector expressing HLA-A*24:02-restricted and Wilms' tumor 1 (WT1)-specific TCR-α/β genes and siRNAs for endogenous TCRs (WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells), we examined the utility of this strategy.
423 26104661 WT1-siTCR/CD4(+) T cells sufficiently recognized leukemia cells in an HLA class I-restricted manner and provided target-specific Th1 help for WT1-siTCR/CD8(+) T cells.
424 26104661 By using a xenografted mouse model, we found that WT1-siTCR/CD4(+) T cells migrated to leukemia sites and subsequently attracted WT1-siTCR/CD8(+) T cells via chemotaxis.
425 26104661 Therapy-oriented experiments revealed effective enhancement of leukemia suppression mediated by concomitant administration of WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells.
426 26104661 Importantly, this augmented efficacy in the presence of WT1-siTCR/CD4(+) T cells was correlated with longer survival and enhanced formation of memory T cells by WT1-siTCR/CD8(+) T cells.
427 26104661 Antileukemia multifunctionality of CD4(+) T cells genetically engineered by HLA class I-restricted and WT1-specific T-cell receptor gene transfer.
428 26104661 To develop gene-modified T-cell-based antileukemia adoptive immunotherapy, concomitant administration of CD4(+) and CD8(+) T cells that have been gene modified using identical HLA class I-restricted leukemia antigen-specific T-cell receptor (TCR) gene transfer has not yet been fully investigated.
429 26104661 Here, using CD4(+) and CD8(+) T cells that had been gene modified with a retroviral vector expressing HLA-A*24:02-restricted and Wilms' tumor 1 (WT1)-specific TCR-α/β genes and siRNAs for endogenous TCRs (WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells), we examined the utility of this strategy.
430 26104661 WT1-siTCR/CD4(+) T cells sufficiently recognized leukemia cells in an HLA class I-restricted manner and provided target-specific Th1 help for WT1-siTCR/CD8(+) T cells.
431 26104661 By using a xenografted mouse model, we found that WT1-siTCR/CD4(+) T cells migrated to leukemia sites and subsequently attracted WT1-siTCR/CD8(+) T cells via chemotaxis.
432 26104661 Therapy-oriented experiments revealed effective enhancement of leukemia suppression mediated by concomitant administration of WT1-siTCR/CD4(+) T cells and WT1-siTCR/CD8(+) T cells.
433 26104661 Importantly, this augmented efficacy in the presence of WT1-siTCR/CD4(+) T cells was correlated with longer survival and enhanced formation of memory T cells by WT1-siTCR/CD8(+) T cells.
434 26377084 These include vaccine approaches to elicit strong specific immune responses to tumor antigens such as WT-1, HER2 and NY-ESO-1, approaches involving adoptive transfer of in vitro-expanded, naturally arising or genetically engineered tumor-specific lymphocytes, therapeutic administration of monoclonal antibodies to target and eliminate tumor cells, and approaches that inhibit or destroy the molecular or cellular mediators of cancer-induced immunosuppression, such as CTLA-4, PD-1 or Treg cells.
435 26451309 It is our goal to develop a powerful and safe immune therapeutic strategy composed of CB-HCT followed by vaccination with CB CD34+-derived dendritic cells (DCs) presenting the oncoprotein Wilms Tumor-1 (WT1), which is expressed in AML-blasts in the majority of patients.