Costimulation provided by DNA immunization enhances antitumor immunity.
The interaction of the TCR with MHC class I-bound Ag is insufficient for the priming of CTL unless secondary costimulatory signals are provided. To ascertain the minimum elements required to activate an Ag-specific CTL response in vivo, we injected mice intradermally or i.m. with plasmid DNA encoding a MHC class I-restricted peptide Ag (minigene) and different membrane-bound costimulatory ligands. The minigene-encoded epitope only primed a specific CTL response if injected in the vicinity of an ectopically expressed costimulatory ligand. Vector encoding B7-1 was repeatedly more potent at stimulating a cytolytic response than vector encoding B7-2. In contrast the B7-2-encoding plasmid preferentially enhanced Ag-specific Ab responses when injected with either protein or a cDNA expression vector. Gene vaccination with plasmids encoding OVA and B7-1, but not B7-2, prolonged survival in mice challenged with an OVA-transfected tumor. These results show that functional B7-1 transfection can be achieved in vivo and induces the selective induction of CTL. The data suggest that B7-1 plasmids should be coadministered with naked DNA vaccines that aim to induce tumor-specific cellular immunity.
Corr
M
M
Department of Medicine, The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla 92093-0663, USA.
Tighe
H
H
Lee
D
D
Dudler
J
J
Trieu
M
M
Brinson
D C
DC
Carson
D A
DA
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D051940:B7-2 Antigen; D004247:DNA / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010047:Ovalbumin / Q000276:immunology; D010957:Plasmids / Q000276:immunology; D012513:Sarcoma, Experimental; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013945:Thymoma; D014407:Tumor Cells, Cultured; D019139:Tumor Escape / Q000235:genetics* / Q000276:immunology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; D010047:Ovalbumin; D004247:DNA