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

Int J Cancer. 1999 Nov 12;83(4):532-40. doi: 10.1002/(sici)1097-0215(19991112)83:4<532::aid-ijc16>;2-k.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Cytotoxicity Tests, Immunologic
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Immunization
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / immunology
  • Neoplasm Transplantation / immunology
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / pathology
  • T-Lymphocytes, Cytotoxic / immunology
  • Transfection
  • Vaccines, DNA / immunology*
  • gp100 Melanoma Antigen


  • Antigens, Neoplasm
  • Epitopes
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Pmel protein, mouse
  • Vaccines, DNA
  • gp100 Melanoma Antigen