Antitumor immunity elicited by tumor cells transfected with B7-2, a second ligand for CD28/CTLA-4 costimulatory molecules.
We have examined the role of the B7-2 costimulatory molecule, a second ligand for CD28/CTLA-4 counter-receptors, in the induction of antitumor immunity. A plasmid containing murine B7-2 cDNA was transfected into the immunogenic mouse mastocytoma P815 of DBA/2 origin. In contrast to the lethal growth of the wild-type (wt) P815 tumor, B7-2-positive (B7-2+) P815 cells inoculated into syngeneic mice regressed, and immunization of mice with such tumor cells protected them against the challenge of wt P815 tumor. Depletion of CD8+, but not of CD4+, lymphocytes in vivo by specific Abs abolished the regression of B7-2+ P815 tumors. CD8+ cytolytic T cells could be generated from mice immunized with B7-2+ P815. They were found to be MHC class I-restricted and specific for the P815 tumor. In contrast, transfection of the B7-2 gene into the nonimmunogenic MCA102 fibrosarcoma of C57BL/6 origin induced neither tumor regression nor protective immunity. Co-expression on MCA102 cells of B7-2 together with the related costimulator B7-1 also failed to induce immunity to MCA102 tumor. Our results indicate that transfection of B7-2 into tumor cells can improve host response to some tumors, and that the effects seen are similar to those previously observed for B7-1.
Yang
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Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Hellström
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Hellström
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Chen
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D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics*; D051940:B7-2 Antigen; D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology; D060908:CTLA-4 Antigen; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D018796:Immunoconjugates; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D000069594:Abatacept