PMID- 10508491
OWN - NLM
STAT- MEDLINE
DCOM- 19991118
LR  - 20191210
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 83
IP  - 4
DP  - 1999 Nov 12
TI  - 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.
PG  - 532-40
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-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.
CI  - Copyright 1999 Wiley-Liss, Inc.
FAU - Yang, S
AU  - Yang S
AD  - Department of Surgery, Duke University Medical Center, Durham, North Carolina 
      27710, USA.
FAU - Vervaert, C E
AU  - Vervaert CE
FAU - Burch, J Jr
AU  - Burch J Jr
FAU - Grichnik, J
AU  - Grichnik J
FAU - Seigler, H F
AU  - Seigler HF
FAU - Darrow, T L
AU  - Darrow TL
LA  - eng
GR  - R01-CA64949/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Epitopes)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (PMEL protein, human)
RN  - 0 (Pmel protein, mouse)
RN  - 0 (Vaccines, DNA)
RN  - 0 (gp100 Melanoma Antigen)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/biosynthesis/genetics/immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cells, Cultured
MH  - Cytotoxicity Tests, Immunologic
MH  - Dendritic Cells/*immunology/metabolism
MH  - Epitopes/genetics/immunology
MH  - Female
MH  - Immunization
MH  - Membrane Glycoproteins/biosynthesis/*genetics/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasm Proteins/biosynthesis/*genetics/immunology
MH  - Neoplasm Transplantation/immunology
MH  - Neoplasms, Experimental/*immunology/pathology
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transfection
MH  - Vaccines, DNA/*immunology
MH  - gp100 Melanoma Antigen
EDAT- 1999/10/03 00:00
MHDA- 1999/10/03 00:01
CRDT- 1999/10/03 00:00
PHST- 1999/10/03 00:00 [pubmed]
PHST- 1999/10/03 00:01 [medline]
PHST- 1999/10/03 00:00 [entrez]
AID - 10.1002/(SICI)1097-0215(19991112)83:4<532::AID-IJC16>3.0.CO;2-K [pii]
AID - 10.1002/(sici)1097-0215(19991112)83:4<532::aid-ijc16>3.0.co;2-k [doi]
PST - ppublish
SO  - Int J Cancer. 1999 Nov 12;83(4):532-40. doi: 
      10.1002/(sici)1097-0215(19991112)83:4<532::aid-ijc16>3.0.co;2-k.