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 language | English |
|---|---|
| Pages (from-to) | 532-540 |
| Number of pages | 9 |
| Journal | International Journal of Cancer |
| Volume | 83 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 28 1999 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - 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
AU - Yang, Sixun
AU - Vervaert, Carol E.
AU - Burch, James
AU - Grichnik, James M
AU - Seigler, Hilliard F.
AU - Darrow, Timothy L.
PY - 1999/10/28
Y1 - 1999/10/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032869074&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032869074&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0215(19991112)83:4<532::AID-IJC16>3.0.CO;2-K
DO - 10.1002/(SICI)1097-0215(19991112)83:4<532::AID-IJC16>3.0.CO;2-K
M3 - Article
C2 - 10508491
AN - SCOPUS:0032869074
VL - 83
SP - 532
EP - 540
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 4
ER -