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
✍ Scribed by Sixun Yang; Carol E. Vervaert; James Burch; Jr.; James Grichnik; Hilliard F. Seigler; Timothy L. Darrow
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 196 KB
- Volume
- 83
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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 liposomemediated 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, MHCrestricted 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. Antibodymediated 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 DNAbased vaccines for immunotherapy and could provide an alternative strategy for tumor vaccine design.