Murine dendritic cells transfected with human GP100 elicit both antigen-specific CD8+ and CD4+ T-cell responses and are more effective than DNA vaccines at generating anti-tumor immunity
| العنوان: | Murine dendritic cells transfected with human GP100 elicit both antigen-specific CD8+ and CD4+ T-cell responses and are more effective than DNA vaccines at generating anti-tumor immunity |
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| المؤلفون: | Carol E. Vervaert, Timothy L. Darrow, James M. Grichnik, Hilliard F. Seigler, James A. Burch, Sixun Yang |
| المصدر: | International Journal of Cancer. 83:532-540 |
| بيانات النشر: | Wiley, 1999. |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | Cancer Research, Cellular immunity, chemical and pharmacologic phenomena, Dendritic cell, Biology, Virology, DNA vaccination, Immune system, Oncology, Antigen, Naked DNA, Cancer research, Cytotoxic T cell, CD8 |
| الوصف: | Dendritic cells (DCs) are potent inducers of cytotoxic T lymphocytes (CTLs) when pulsed with an antigenic peptide or tumor lysate. In this report, we have used liposome-mediated gene transfer to examine the ability of plasmid DNA encoding the human melanoma-associated antigen gp100 to elicit CD8(+) and CD4(+) T-cell responses. We also compared the efficacy between gp100 gene-modified DCs and naked DNA (pCDNA3/gp100)-based vaccines at inducing anti-tumor immunity. DCs were generated from murine bone marrow and transfected in vitro with plasmid DNA containing the gp100 gene. These gp100-modified DCs (DC/gps) were used to stimulate syngeneic naive spleen T cells in vitro or to immunize mice in vivo. Antigen-specific, MHC-restricted CTLs were generated when DC/gps were used to prime T cells both in vitro and in vivo. Thus, these CTLs were cytolytic for gp100-transfected syngeneic (H-2(b)) tumor MCA106 (MCA/gp) and vaccinia-pMel17/gp100-infected syngeneic B16 and MCA106, but not parental tumor MCA106 and B16, or gp100-transfected allogeneic tumor P815 (H-2(d)). Immunization with DC/gp protected mice from subsequent challenge with MCA/gp but not parental MCA106. Antibody-mediated T-cell subset depletion experiments demonstrate that induction of CTLs in vivo is dependent on both CD4(+) and CD8(+) T cells. Furthermore, DC/gp immunization elicits an antigen-specific CD4(+) T-cell response, suggesting that DC/gps present MHC class II epitopes to CD4(+) T cells. In addition, our data show that gene-modified, DC-based vaccines are more effective than the naked DNA-based vaccines at eliciting anti-tumor immunity in both prophylactic and therapeutic models. These results suggest that the use of DCs transfected with plasmid DNA containing a gene for TAA may be superior to peptide-pulsed DCs and naked DNA-based vaccines for immunotherapy and could provide an alternative strategy for tumor vaccine design. |
| تدمد: | 1097-0215 0020-7136 |
| DOI: | 10.1002/(sici)1097-0215(19991112)83:4<532::aid-ijc16>3.0.co;2-k |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::549996d3b92d1e3244034a85dd6c2fa7 https://doi.org/10.1002/(sici)1097-0215(19991112)83:4<532::aid-ijc16>3.0.co;2-k |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........549996d3b92d1e3244034a85dd6c2fa7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10970215 00207136 |
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| DOI: | 10.1002/(sici)1097-0215(19991112)83:4<532::aid-ijc16>3.0.co;2-k |