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PMID |
Sentence |
1 |
9764850
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To assess antibody responses to potential melanoma/melanocyte autoantigens, the open-reading frame sequences of tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, and melanoma-associated glycoprotein antigen family (gp100/pmel17) genes were cloned and expressed as recombinant proteins in E. coli.
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2 |
9856813
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We examined antibody responses to a melanocyte autoantigen, tyrosinase-related protein-2 (TRP-2), as it is highly expressed in cutaneous melanoma and melanocytes.
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3 |
10078966
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Of perhaps greater clinical interest, genetic immunization using cDNA encoding the normal, germline-encoded murine melanosomal protein tyrosinase-related protein-2 (TRP-2) resulted in delayed outgrowth of TRP-2+ B16 melanoma in mice and was associated with an in vivo activation of TRP-2-specific cytotoxic T lymphocytes.
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4 |
10340547
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Mouse bone marrow-derived DCs were genetically modified with lymphotactin (Lptn) by adenovirus vector, which conferred on DCs preferential chemotaxis to CD4+ and CD8+ T cells (Cao et al., 1998).
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5 |
10340547
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In both tumor models, immunization with 4 X 10(4) tumor RNA-pulsed Lptn-DCs induced more potent CTL activity, compared with their counterparts, specifically against tumor cells and Mut1 or tyrosinase-related protein 2 (TRP-2) peptide-pulsed RMA-S cells, and rendered the immunized mice resistant to tumor challenge much more effectively.
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6 |
10340547
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CD8+ T cells were necessary and sufficient to generate the protection of Lptn-DC-based RNA tumor vaccines, and CD4+ T cells were required for the induction of tumor rejection.
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7 |
10728600
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Genetic immunization of mice with human TRP2 resulted in coat depigmentation as a sign of autoimmune-mediated destruction of melanocytes and provided significant protection against metastatic growth of B16 melanoma Induction of protective immunity was associated with TRP2-reactive antibodies and CD8+ T cells.
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8 |
10779556
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We demonstrated that peripheral T cell tolerance toward murine melanoma self-antigens gp100 and TRP-2 can be broken by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to minigenes encoding peptide epitopes gp100(25-33) and TRP-2(181-188).
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9 |
10779556
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These epitopes contain dominant anchor residues for MHC class I antigen alleles H-2D(b) and H-2K(b), respectively.
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10 |
10779556
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Tumor-protective immunity was mediated by MHC class I antigen-restricted CD8(+) T cells that secreted T(H)1 cytokine IFN-gamma and induced tumor rejection and growth suppression after a lethal challenge with B16G3. 26 murine melanoma cells.
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11 |
11221870
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Therapeutic tumor immunity induced by polyimmunization with melanoma antigens gp100 and TRP-2.
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12 |
11221870
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Splenocytes from combination-immunized animals killed syngeneic targets loaded with peptides derived from both gp100 and TRP-2.
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13 |
11221870
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Therapeutic tumor immunity induced by polyimmunization with melanoma antigens gp100 and TRP-2.
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14 |
11221870
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Splenocytes from combination-immunized animals killed syngeneic targets loaded with peptides derived from both gp100 and TRP-2.
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15 |
11507070
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We demonstrate that a mouse-human chimeric anti-ganglioside GD2-interleukin (IL)-2 fusion protein (ch14.18-IL2) substantially amplifies tumor-protective immunity against murine melanoma induced by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to murine melanoma peptide epitopes gp100(25-35) and TRP-2(181-188).
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16 |
11507070
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The tumor-protective immunity was mediated by MHC class I antigen- restricted CD8(+) T cells together with CD4(+) T cell help, which was required only for tumor cell killing in the effector phase of the immune response.
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17 |
11507070
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The immunological mechanisms involved in this antitumor effect were suggested by a decisively increased secretion of tumor necrosis factor alpha TNFTnTNa and IFN-gamma from CD4(+) and CD8(+) T cells and a markedly up-regulated expression on CD8(+) T cells of high-affinity IL-2 receptor alpha chain (CD25), costimulatory molecule CD28, and adhesion molecule lymphocyte function-associated antigen-2 (LFA-2/CD2).
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18 |
11863419
|
We developed a polyvalent melanoma gene vaccine using a plasmid vector to deliver the immunogenic human melanoma-associated antigens (MAAs) gp100 and TRP-2.
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19 |
11863419
|
Although both i.m. and i.n. immunization induced Th1 (T helper) and Th2 cell responses to gp100 and TRP2, the i.m. route induced a better Th1 response.
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20 |
11863419
|
We developed a polyvalent melanoma gene vaccine using a plasmid vector to deliver the immunogenic human melanoma-associated antigens (MAAs) gp100 and TRP-2.
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21 |
11863419
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Although both i.m. and i.n. immunization induced Th1 (T helper) and Th2 cell responses to gp100 and TRP2, the i.m. route induced a better Th1 response.
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22 |
12672050
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Dendritic cells transduced with TAT protein transduction domain-containing tyrosinase-related protein 2 vaccinate against murine melanoma.
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23 |
12672050
|
Here we studied B16 melanoma in C57BL/6 mice, using murine tyrosinase-related protein 2 (Trp2) as a candidate tumor Ag.
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24 |
12672050
|
Trp2(180-188) peptide-pulsed DC protected 35% of recipients, and irradiated GM-CSF-producing B16 cells protected 75%. rTAT-PTD-Trp2Delta-transduced DC induced a more vigorous memory response to B16 rechallenge than the other regimens, and protected 30% of recipients from progressive tumor development in treatment studies.
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25 |
12672050
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In this setting, Trp2 peptide-treated DC protected 20% and irradiated GM-CSF-producing cells protected 0%.
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26 |
12672050
|
Dendritic cells transduced with TAT protein transduction domain-containing tyrosinase-related protein 2 vaccinate against murine melanoma.
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27 |
12672050
|
Here we studied B16 melanoma in C57BL/6 mice, using murine tyrosinase-related protein 2 (Trp2) as a candidate tumor Ag.
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28 |
12672050
|
Trp2(180-188) peptide-pulsed DC protected 35% of recipients, and irradiated GM-CSF-producing B16 cells protected 75%. rTAT-PTD-Trp2Delta-transduced DC induced a more vigorous memory response to B16 rechallenge than the other regimens, and protected 30% of recipients from progressive tumor development in treatment studies.
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29 |
12672050
|
In this setting, Trp2 peptide-treated DC protected 20% and irradiated GM-CSF-producing cells protected 0%.
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30 |
12672050
|
Dendritic cells transduced with TAT protein transduction domain-containing tyrosinase-related protein 2 vaccinate against murine melanoma.
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31 |
12672050
|
Here we studied B16 melanoma in C57BL/6 mice, using murine tyrosinase-related protein 2 (Trp2) as a candidate tumor Ag.
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32 |
12672050
|
Trp2(180-188) peptide-pulsed DC protected 35% of recipients, and irradiated GM-CSF-producing B16 cells protected 75%. rTAT-PTD-Trp2Delta-transduced DC induced a more vigorous memory response to B16 rechallenge than the other regimens, and protected 30% of recipients from progressive tumor development in treatment studies.
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33 |
12672050
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In this setting, Trp2 peptide-treated DC protected 20% and irradiated GM-CSF-producing cells protected 0%.
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34 |
12747770
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Tyrosinase-related proteins-1 and -2 (gp75/TRP-1 and TRP-2) are melanosomal membrane glycoproteins recognized by antibodies and T-cells from patients with melanoma.
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35 |
12747770
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These results show that immunity to TRP-2 following DNA immunization uses an IFN-gamma-dependent Th1 pathway, but immunity to gp75/TRP-1 is down-regulated by IFN-gamma.
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36 |
12747770
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Tyrosinase-related proteins-1 and -2 (gp75/TRP-1 and TRP-2) are melanosomal membrane glycoproteins recognized by antibodies and T-cells from patients with melanoma.
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37 |
12747770
|
These results show that immunity to TRP-2 following DNA immunization uses an IFN-gamma-dependent Th1 pathway, but immunity to gp75/TRP-1 is down-regulated by IFN-gamma.
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38 |
12944987
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A mouse glioblastoma cell line, termed GL261, was shown to express high levels of proteins involved in melanin biosynthesis such as the tyrosinase-related protein-2 (TRP-2), which is commonly overexpressed in melanoma cells.
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39 |
12944987
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Mice injected with GL261 cells developed a CD8(+) T-cell response to TRP-2 and a DNA vaccine expressing human (h)TRP-2 induced CD8(+) T cells that recognized TRP-2 expressed by GL261 cells indicating that this melanoma-associated antigen may be suited for active immunotherapy of glioblastoma.
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40 |
12944987
|
Vaccine-induced protection against intracerebral challenge required both CD4(+) and CD8(+) T cells.
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41 |
14679014
|
In this study, we provide evidence that two common murine glioma cell lines (GL26 and GL261) express the melanoma antigens gp100 and tyrosinase-related protein 2 (TRP-2).
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42 |
14679014
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Lastly, mice that were prevaccinated with human gp100 and TRP-2 peptide-pulsed dendritic cells had significantly extended survival when challenged with tumor cells in the brain, resulting in >50% long-term survival.
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43 |
14679014
|
In this study, we provide evidence that two common murine glioma cell lines (GL26 and GL261) express the melanoma antigens gp100 and tyrosinase-related protein 2 (TRP-2).
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44 |
14679014
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Lastly, mice that were prevaccinated with human gp100 and TRP-2 peptide-pulsed dendritic cells had significantly extended survival when challenged with tumor cells in the brain, resulting in >50% long-term survival.
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45 |
15603192
|
Using five defined human T cell lines derived from melanoma patients, allogeneic DCs of HLA-A2, HLA-DR4 and HLA-DR7 haplotypes fused with MART-1, gp100, tyrosinase and TRP-2 expressing 888 mel melanoma cells were analysed for their ability to stimulate specific cytokine (IFN-gamma and GM-CSF) secretion.
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46 |
15603192
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DC-888 mel hybrids presented all tumour-associated epitopes to both CD4 and CD8 T cell lines in the context of MHC class II and I molecules, respectively.
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47 |
15726359
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Results showed that TRP-2 epitope-expressing IFN-gamma decreased B16 tumorigenicity and enhanced its immunogenicity after gene transfer.
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48 |
15781661
|
Administration of IFN-alpha enhances the efficacy of a granulocyte macrophage colony stimulating factor-secreting tumor cell vaccine.
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49 |
15781661
|
The studies reported herein show that 50% of mice reject established B16 tumors following treatment with the combination of a granulocyte macrophage colony-stimulating factor-secreting tumor cell vaccine (B16.GM) and subclinical doses of recombinant murine IFN-alpha delivered at the vaccine site.
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50 |
15781661
|
Furthermore, a 30-fold increase in the frequency of melanoma-associated antigen (Trp-2 and gp100) specific T cells was observed in mice treated with the combination when compared with unvaccinated controls.
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51 |
15781661
|
These data show that IFN-alpha combined with a granulocyte macrophage colony-stimulating factor-secreting tumor cell vaccine significantly enhances vaccine potency and may represent a potential new approach for tumor immunotherapy.
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52 |
15913853
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Characterization of anti-self CD8 T-cell responses stimulated by recombinant Listeria monocytogenes expressing the melanoma antigen TRP-2.
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53 |
15913853
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We constructed a recombinant strain of Listeria monocytogenes (rLM) expressing murine tyrosinase-related protein-2 (TRP-2), a nonmutated melanocyte-derived differentiation antigen highly expressed in melanomas.
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54 |
15913853
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Immunization of C57Bl/6 mice with this rLM strain efficiently primed CD8 T cells to recognize the MHC class I-restricted TRP-2180-188 epitope and express IFN-gamma upon in vitro peptide stimulation.
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55 |
16061687
|
To exploit these properties for immunization purposes, we conjugated the melanoma antigen tyrosinase-related protein (TRP)-2 to alphaDEC-205 antibodies and immunized mice with these conjugates together with dendritic cell-activating oligonucleotides (CpG).
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56 |
16061687
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Approximately 70% of the animals were cured from existing tumors by treatment with alphaDEC conjugates carrying two different melanoma antigens (TRP-2 and gp100).
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57 |
16061687
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This protection was due to induction of melanoma-specific CD4 and CD8 responses.
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58 |
16112911
|
Enhancement of immunity by a DNA melanoma vaccine against TRP2 with CCL21 as an adjuvant.
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59 |
16112911
|
Recent studies have suggested that a chemokine ligand for the CCR7 (CCL21) present on T-cells and dendritic cells is important in activating and regulating immunity.
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60 |
16259559
|
Compared with a naked DNA tyrosinase-related protein-2 (TRP2)-heat shock protein-70 (hsp70) vaccine, the TRP2-specific interferon-gamma-producing CD8+ T cell response was augmented by direct in vivo administration of an LV-TRP2hsp70 vaccine, which induced significant therapeutic antitumor immunity in subcutaneous B16 and subcutaneous GL-26 models.
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61 |
16580737
|
Fusion protein of ATPase domain of Hsc70 with TRP2 acting as a tumor vaccine against B16 melanoma.
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62 |
16699372
|
Using a peptide from the melanocyte differentiation antigen tyrosinase-related protein (TRP2) 2 we could show that vaccination with liposome-encapsulated peptide in combination with oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODNs) as adjuvant leads to the induction of tumor cell-specific cytotoxic T cells.
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63 |
17142789
|
Synergism between CpG-containing oligodeoxynucleotides and IL-2 causes dramatic enhancement of vaccine-elicited CD8+ T cell responses.
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64 |
17142789
|
When we administered therapeutic vaccines containing the MHC class I-presented self-peptide tyrosinase-related protein (TRP)-2(180-188) and CpG-containing oligodeoxynucleotides (CpG ODN) to mice, growth of the TRP-2-expressing B16F1 melanoma was not inhibited compared with growth in mice that received control vaccinations.
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65 |
17142789
|
When we added systemic IL-2 to the TRP-2(180-188) plus CpG ODN vaccines, growth of B16F1 was inhibited in a CD8-dependent, epitope-specific manner.
|
66 |
17142789
|
The antitumor efficacy of the different regimens correlated with their ability to elicit TRP-2(180-188)-specific CD8+ T cell responses.
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67 |
17142789
|
When we administered TRP-2(180-188) plus CpG ODN-containing vaccines with systemic IL-2, 18.2% of CD8+ T cells were specific for TRP-2(180-188).
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68 |
17142789
|
Identical TRP-2(180-188) plus CpG ODN vaccines given without IL-2 elicited a TRP-2(180-188)-specific CD8+ T cell response of only 1.1% of CD8+ T cells.
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69 |
17142789
|
Vaccines containing TRP-2(180-188) without CpG ODN elicited TRP-2(180-188)-specific responses of 2.8% of CD8+ T cells when administered with IL-2.
|
70 |
17142789
|
There was up to a 221-fold increase in the absolute number of TRP-2(180-188)-specific CD8+ T cells when IL-2 was added to TRP-2(180-188) plus CpG ODN-containing vaccines.
|
71 |
17142789
|
Peptide plus CpG ODN vaccines administered with IL-2 generated epitope-specific CD8+ T cells by a mechanism that depended on endogenous IL-6.
|
72 |
17142789
|
Synergism between CpG-containing oligodeoxynucleotides and IL-2 causes dramatic enhancement of vaccine-elicited CD8+ T cell responses.
|
73 |
17142789
|
When we administered therapeutic vaccines containing the MHC class I-presented self-peptide tyrosinase-related protein (TRP)-2(180-188) and CpG-containing oligodeoxynucleotides (CpG ODN) to mice, growth of the TRP-2-expressing B16F1 melanoma was not inhibited compared with growth in mice that received control vaccinations.
|
74 |
17142789
|
When we added systemic IL-2 to the TRP-2(180-188) plus CpG ODN vaccines, growth of B16F1 was inhibited in a CD8-dependent, epitope-specific manner.
|
75 |
17142789
|
The antitumor efficacy of the different regimens correlated with their ability to elicit TRP-2(180-188)-specific CD8+ T cell responses.
|
76 |
17142789
|
When we administered TRP-2(180-188) plus CpG ODN-containing vaccines with systemic IL-2, 18.2% of CD8+ T cells were specific for TRP-2(180-188).
|
77 |
17142789
|
Identical TRP-2(180-188) plus CpG ODN vaccines given without IL-2 elicited a TRP-2(180-188)-specific CD8+ T cell response of only 1.1% of CD8+ T cells.
|
78 |
17142789
|
Vaccines containing TRP-2(180-188) without CpG ODN elicited TRP-2(180-188)-specific responses of 2.8% of CD8+ T cells when administered with IL-2.
|
79 |
17142789
|
There was up to a 221-fold increase in the absolute number of TRP-2(180-188)-specific CD8+ T cells when IL-2 was added to TRP-2(180-188) plus CpG ODN-containing vaccines.
|
80 |
17142789
|
Peptide plus CpG ODN vaccines administered with IL-2 generated epitope-specific CD8+ T cells by a mechanism that depended on endogenous IL-6.
|
81 |
17142789
|
Synergism between CpG-containing oligodeoxynucleotides and IL-2 causes dramatic enhancement of vaccine-elicited CD8+ T cell responses.
|
82 |
17142789
|
When we administered therapeutic vaccines containing the MHC class I-presented self-peptide tyrosinase-related protein (TRP)-2(180-188) and CpG-containing oligodeoxynucleotides (CpG ODN) to mice, growth of the TRP-2-expressing B16F1 melanoma was not inhibited compared with growth in mice that received control vaccinations.
|
83 |
17142789
|
When we added systemic IL-2 to the TRP-2(180-188) plus CpG ODN vaccines, growth of B16F1 was inhibited in a CD8-dependent, epitope-specific manner.
|
84 |
17142789
|
The antitumor efficacy of the different regimens correlated with their ability to elicit TRP-2(180-188)-specific CD8+ T cell responses.
|
85 |
17142789
|
When we administered TRP-2(180-188) plus CpG ODN-containing vaccines with systemic IL-2, 18.2% of CD8+ T cells were specific for TRP-2(180-188).
|
86 |
17142789
|
Identical TRP-2(180-188) plus CpG ODN vaccines given without IL-2 elicited a TRP-2(180-188)-specific CD8+ T cell response of only 1.1% of CD8+ T cells.
|
87 |
17142789
|
Vaccines containing TRP-2(180-188) without CpG ODN elicited TRP-2(180-188)-specific responses of 2.8% of CD8+ T cells when administered with IL-2.
|
88 |
17142789
|
There was up to a 221-fold increase in the absolute number of TRP-2(180-188)-specific CD8+ T cells when IL-2 was added to TRP-2(180-188) plus CpG ODN-containing vaccines.
|
89 |
17142789
|
Peptide plus CpG ODN vaccines administered with IL-2 generated epitope-specific CD8+ T cells by a mechanism that depended on endogenous IL-6.
|
90 |
17375074
|
We programmed mouse bone marrow (BM) cells with lentiviral vectors (LV-GI4) so that they produced granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in an autonomous manner.
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91 |
17375074
|
The immunostimulatory efficacy of DC/LV-GI4 cells was evaluated using MART1 and TRP2 as co-expressed melanoma antigens.
|
92 |
18076066
|
In this article, we report that the melanocyte differentiation antigen TRP2 (tyrosinase-related protein 2) is not predominantly involved in the tumor rejection of a syngeneic murine glioma.
|
93 |
18680779
|
Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8+ T cell-mediated anti-tumor immunity.
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94 |
18680779
|
Vaccination of mice bearing melanoma B16 tumors with PLGA nanoparticles (NP) co-encapsulating the poorly immunogenic melanoma antigen, tyrosinase-related protein 2 (TRP2), along with Toll-like receptor (TLR) ligand (7-acyl lipid A) was examined.
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95 |
18680779
|
Activated TRP2-specific CD8 T cells were capable of interferon (IFN)-gamma secretion at lymph nodes and spleens of the vaccinated mice.
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96 |
18807035
|
ABT-737, a small molecule inhibitor of the antiapoptotic proteins Bcl-2, Bcl-w and Bcl-x(L), was tested for the ability to increase antitumor immune responses in two tumor immunotherapy animal models.
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97 |
18807035
|
However, the addition of ABT-737 to either a vaccine strategy involving priming with TRP-2 melanoma antigen peptide-pulsed DC and boosting with recombinant Listeria monocytogenes expressing the same melanoma antigen, or the adoptive transfer of TCR transgenic cells, did not result in superior antitumor activity against B16 murine melanoma.
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98 |
18807035
|
In vitro studies failed to demonstrate increased cytotoxic lytic activity when testing the combination of ABT-737 with lymphokine activated killer (LAK) cells, or the death receptor agonists Fas, TRAIL-ligand or TNF-alpha against the CT26 and B16 cell lines.
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99 |
19238011
|
Tyrosinase-related protein 2 (TRP-2) is a melanogenic enzyme expressed by both melanocytes and melanomas that is reported to be a candidate melanoma rejection antigen.
|
100 |
19238011
|
To study the role of self-reactive CD8+ T cells in tumor immunity and autoimmunity, we generated mice that bear a T-cell receptor transgene (TCR Tg) specific for the TRP-2(180-188) epitope.
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101 |
19238011
|
Tyrosinase-related protein 2 (TRP-2) is a melanogenic enzyme expressed by both melanocytes and melanomas that is reported to be a candidate melanoma rejection antigen.
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102 |
19238011
|
To study the role of self-reactive CD8+ T cells in tumor immunity and autoimmunity, we generated mice that bear a T-cell receptor transgene (TCR Tg) specific for the TRP-2(180-188) epitope.
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103 |
19787240
|
By using electroporation-mediated gene/pDNA delivery, the anti-tumor efficacy of vaccination with pDNAs encoding gp100, TRP2 and Ii-PADRE was facilitated by administration of soluble form of EphB4 fused with human serum albumin (sEphB4-HSA), or by co-delivery of pDNAs encoding Angiostatin and/or Endostatin.
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104 |
20937315
|
The adjuvant effects of the TLR7 agonist, imiquimod, and the TLR9 agonist, ODN1826, were tested with rAAV expressing the melanoma antigen, Trp2.
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105 |
20937315
|
TLR7 and TLR9 agonists can be used to enhance the immune response to rAAV immunogens, but antagonism can be observed when combined.
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106 |
21157438
|
Consequently, the cytosolic DNA sensor, DNA-dependent activator of interferon (IFN) regulatory factors (DAI), was used as a genetic adjuvant.
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107 |
21157438
|
In vivo electroporation (EP) of mice with a DAI-encoding plasmid (pDAI) promoted transcription of genes encoding type I IFNs, proinflammatory cytokines, and costimulatory molecules.
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108 |
21157438
|
Moreover, codelivery of pDAI effectively promoted CTL and CD4(+) Th1 responses to the TAA survivin.
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109 |
21157438
|
The DAI-enhanced CTL induction required nuclear factor κB (NF-κB) activation and type I IFN signaling, but did not involve the IFN regulatory factor 3 (IRF3).
|
110 |
21157438
|
Codelivery of pDAI also increased CTL responses to the melanoma-associated antigen tyrosinase-related protein-2 (TRP2), enhanced tumor rejection and conferred long-term protection against B16 melanoma challenge.
|
111 |
21250746
|
Following immunization using US exposure and Man-PEG(2000) bubble lipoplexes constructed with pUb-M, which expresses ubiquitylated melanoma-specific antigens (gp100 and TRP-2), the secretion of Th1 cytokines (IFN-γ and TNF-α) and the activities of cytotoxic T lymphocytes (CTLs) were specifically enhanced in the presence of B16BL6 melanoma antigens.
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112 |
21327126
|
Using an inducible and rapid expression plasmid, vaccination with several antigens of different length and epitope composition, including TRp-2, gp100 and MUC18, was evaluated against glioma tumor cells.
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113 |
21327126
|
Characteristics that consistently improved anti-tumor immunity include: long peptides with immunodominant and cryptic CD8(+) epitopes, and strong CD4(+) Th epitopes.
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114 |
21464590
|
Ex vivo assays using immunized mice demonstrated that CIITA-Exo induced a higher amount of Th1-polarized immune responses such as Th1-type IgG2a antibodies and IFN-γ cytokine as well as TRP2-specific CD8+ T cells.
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115 |
21479379
|
Suppressor of cytokine signaling-1 (SOCS1) is a key negative regulator of the JAK/STAT signal pathway and plays an essential role in suppressing systemic autoimmunity that is mediated by DCs.
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116 |
21479379
|
In the mouse melanoma model, we found that a 2x106 TRP2-pulsed DC vaccine was able to induce immune tolerance, while a 2x106 SOCS1-silenced DC/TRP2 vaccine prevented immune tolerance.
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117 |
21479379
|
Further experiments revealed that activation-induced T cell death (AICD) through the Fas/Fas-L pathway may play a crucial role in immune tolerance induced by 2x106 TRP2-pulsed DC.
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118 |
21479379
|
SOCS1-silencing in DCs could prevent immune tolerance by inhibiting Fas and Fas-L expression, induced by an increase in IL-12p70 and IL-6 production.
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119 |
21479379
|
In addition, in 2x106 SOCS1-silenced DC/TRP2 immunized mice, higher levels of IL-12p70 and IFN-γ and lower IL-17 production may inhibit tumor angiogenesis and therefore assist in breaking immune tolerance.
|
120 |
21479379
|
Suppressor of cytokine signaling-1 (SOCS1) is a key negative regulator of the JAK/STAT signal pathway and plays an essential role in suppressing systemic autoimmunity that is mediated by DCs.
|
121 |
21479379
|
In the mouse melanoma model, we found that a 2x106 TRP2-pulsed DC vaccine was able to induce immune tolerance, while a 2x106 SOCS1-silenced DC/TRP2 vaccine prevented immune tolerance.
|
122 |
21479379
|
Further experiments revealed that activation-induced T cell death (AICD) through the Fas/Fas-L pathway may play a crucial role in immune tolerance induced by 2x106 TRP2-pulsed DC.
|
123 |
21479379
|
SOCS1-silencing in DCs could prevent immune tolerance by inhibiting Fas and Fas-L expression, induced by an increase in IL-12p70 and IL-6 production.
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124 |
21479379
|
In addition, in 2x106 SOCS1-silenced DC/TRP2 immunized mice, higher levels of IL-12p70 and IFN-γ and lower IL-17 production may inhibit tumor angiogenesis and therefore assist in breaking immune tolerance.
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125 |
22120194
|
We reason that a strategy capable of improving CD8+ T cell activation would improve the efficacy of protein-based vaccines, which predominantly generate CD4+ T cell-mediated responses.
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126 |
22120194
|
Herein, we explore the ability of a novel cell-penetrating peptide (CPP), LAH4, to facilitate intracellular delivery of protein-based vaccines adjuvanted with Toll-like receptor 9 agonist CpG oligonucleotide (CpG) to generate enhanced CD8+ T cell immune responses and antitumor effects.
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127 |
22120194
|
Furthermore, we found that LAH4 was able to enhance the ability of a tyrosinase-related protein 2 (TRP-2) peptide-based vaccine to generate TRP2-specific CD8+ T cells and antitumor effects against TRP2-expressing tumors.
|
128 |
22506061
|
Similarly, the enlarged T cell repertoire in AIRE(-/-) mice enables them to mount anti-MAA and anti-melanoma responses as shown by increased anti-melanoma antibodies, and enhanced CD4(+) and MAA-specific CD8(+) T cell responses after melanoma challenge.
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129 |
22506061
|
We show that thymic expression of gp100 is under the control of AIRE, leading to increased gp100-specific CD8(+) T cell frequencies in AIRE(-/-) mice.
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130 |
22506061
|
TRP-2 (tyrosinase-related protein), on the other hand, is absent from TECs and consequently TRP-2 specific CD8(+) T cells were found in both AIRE(-/-) and AIRE(+/+) mice.
|
131 |
23104352
|
We describe here the use of particle-mediated gene transfer for the induction of immune responses against melanoma antigens in murine tumor models using the melanocyte differentiation antigen tyrosinase-related protein 2 (TRP2) as an antigen in a murine B16 melanoma model.
|
132 |
23333935
|
In situ Ad.Flagrp170 therapy provokes systemic activation of CTLs that recognize several antigens naturally expressing in melanoma (e.g., gp100/PMEL and TRP2/DCT).
|
133 |
23333935
|
Antibody neutralization assays show that IL-12 and IFN-γ are essential for the Flagrp170-elicited antitumor response, which also involves CD8(+) T cells and natural killer cells.
|
134 |
24018273
|
To try and understand why this is so, we have generated potent adenoviral vectors encoding the endogenous tumor Ags (TA) tyrosinase-related protein-2 (TRP-2) and glycoprotein 100 (GP100) tethered to the invariant chain (Ii).
|
135 |
24349329
|
To co-target CAFs and tumor cells we developed a new compound DC vaccine that encodes an A20-specific shRNA to enhance DC function, and targets fibroblast activation protein (FAP) expressed in CAFs and the tumor antigen tyrosine-related protein (TRP)2 (DC-shA20-FAP-TRP2).
|
136 |
24349329
|
DC-shA20-FAP-TRP2 vaccination induced robust FAP- and TRP2-specific T-cell responses, resulting in greater antitumor activity in the B16 melanoma model in comparison to monovalent vaccines or a vaccine encoding antigens and a control shRNA.
|
137 |
24795357
|
We have shown that a vaccine based on alphavirus replicon particles (VRP) activates strong cellular and humoral immunity to tyrosinase-related protein-2 (TRP2) melanoma antigen, providing prophylactic and therapeutic effects in stringent mouse models.
|
138 |
24795357
|
Here, we report that the immunogenicity and efficacy of this vaccine is increased in combination with either antagonist anti-CTL antigen-4 (CTLA-4) or agonist anti-glucocorticoid-induced TNF family-related gene (GITR) immunomodulatory monoclonal antibodies (mAb).
|
139 |
24795357
|
These mAbs had similar adjuvant effects in priming an adaptive immune response against the vaccine-encoded antigen, augmenting, respectively, approximately 4- and 2-fold the TRP2-specific CD8(+) T-cell response and circulating Abs, compared with the vaccine alone.
|
140 |
24795357
|
Furthermore, while both mAbs increased the frequency of tumor-infiltrating CD8(+) T cells, anti-CTLA-4 mAb also increased the quantity of intratumor CD4(+)Foxp3(-) T cells expressing the negative costimulatory molecule programmed death-1 (PD-1).
|
141 |
24795357
|
They also indicate that tumor-infiltrating CD4(+)Foxp3(-)PD-1(+) T cells may affect the outcome of immunomodulatory treatments.
|
142 |
24795357
|
We have shown that a vaccine based on alphavirus replicon particles (VRP) activates strong cellular and humoral immunity to tyrosinase-related protein-2 (TRP2) melanoma antigen, providing prophylactic and therapeutic effects in stringent mouse models.
|
143 |
24795357
|
Here, we report that the immunogenicity and efficacy of this vaccine is increased in combination with either antagonist anti-CTL antigen-4 (CTLA-4) or agonist anti-glucocorticoid-induced TNF family-related gene (GITR) immunomodulatory monoclonal antibodies (mAb).
|
144 |
24795357
|
These mAbs had similar adjuvant effects in priming an adaptive immune response against the vaccine-encoded antigen, augmenting, respectively, approximately 4- and 2-fold the TRP2-specific CD8(+) T-cell response and circulating Abs, compared with the vaccine alone.
|
145 |
24795357
|
Furthermore, while both mAbs increased the frequency of tumor-infiltrating CD8(+) T cells, anti-CTLA-4 mAb also increased the quantity of intratumor CD4(+)Foxp3(-) T cells expressing the negative costimulatory molecule programmed death-1 (PD-1).
|
146 |
24795357
|
They also indicate that tumor-infiltrating CD4(+)Foxp3(-)PD-1(+) T cells may affect the outcome of immunomodulatory treatments.
|