ANTITUMOR IMMUNITY ELICITED BY TUMOR-CELLS TRANSFECTED WITH B7-2, A 2ND 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 counterreceptors, in the induction of antitumo r immunity. A plasmid containing murine B7-2 cDNA was transfected into the immunogenic mouse mastocytoma P815 of DBA/2 origin. In contrast t o the lethal growth of the wild-type (wt) P815 tumor, B7-2-positive (B 7-2(+)) P815 cells inoculated into syngeneic mice regressed, and immun ization of mice with such tumor cells protected them against the chall enge of wt P815 tumor. Depletion of CD8(+), but not of CD4(+), lymphoc ytes in vivo by specific Abs abolished the regression of B7-2(+) P815 tumors. CD8(+) cytolytic T cells could be generated from mice immunize d 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 gen e into the nonimmunogenic MCA102 fibrosarcoma of C57BL/6 origin induce d neither tumor regression nor protective immunity. Co-expression on M CA102 cells of B7-2 together with the related costimulator B7-1 also f ailed to induce immunity to MCA102 tumor. Our results indicate that tr ansfection of B7-2 into tumor cells can improve host response to some tumors, and that the effects seen are similar to those previously obse rved for B7-1.