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

Sixun Yang, Carol E. Vervaert, James Burch, James M Grichnik, Hilliard F. Seigler, Timothy L. Darrow

Research output: Contribution to journalArticle

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Abstract

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-2b) tumor MCA106 (MCA/gp) and vaccinia-pMeII7/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.

Original languageEnglish
Pages (from-to)532-540
Number of pages9
JournalInternational Journal of Cancer
Volume83
Issue number4
DOIs
StatePublished - Oct 28 1999
Externally publishedYes

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CD8 Antigens
CD4 Antigens
DNA Vaccines
Dendritic Cells
Immunity
T-Lymphocytes
Neoplasms
Cytotoxic T-Lymphocytes
Plasmids
Genes
DNA
gp100 Melanoma Antigen
Immunization
Vaccines
Vaccinia
Peptides
Cancer Vaccines
T-Lymphocyte Subsets
Helper-Inducer T-Lymphocytes
Liposomes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Yang, Sixun; Vervaert, Carol E.; Burch, James; Grichnik, James M; Seigler, Hilliard F.; Darrow, Timothy L.

In: International Journal of Cancer, Vol. 83, No. 4, 28.10.1999, p. 532-540.

Research output: Contribution to journalArticle

Yang, Sixun ; Vervaert, Carol E. ; Burch, James ; Grichnik, James M ; Seigler, Hilliard F. ; Darrow, Timothy L. / 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. In: International Journal of Cancer. 1999 ; Vol. 83, No. 4. pp. 532-540.
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AU - Seigler, Hilliard F.

AU - Darrow, Timothy L.

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