B7-1 IS SUPERIOR TO B7-2 COSTIMULATION IN THE INDUCTION AND MAINTENANCE OF T-CELL-MEDIATED ANTILEUKEMIA IMMUNITY - FURTHER EVIDENCE THAT B7-1 AND B7-2 ARE FUNCTIONALLY DISTINCT

Although intact, viable tumor cells rarely induce a clinically signifi cant immune response in vivo, immunogenicity can be elicited by irradi ated tumor cells that protect against subsequent challenge with wild-t ype intact viable tumor cells. Genetic modification of murine tumor ce lls, by transfection of cDNAs encoding either cytokines, MHC molecules , or costimulatory molecules, has been capable of inducing antitumor i mmunity, We and others have previously demonstrated that expression of the B7-1 costimulatory molecule, in either immunogenic or nonimmunoge nic tumors, can protect against subsequent challenge with wild-type tu mor cells. In this work, using a murine model of acute myeloid leukemi a, we demonstrate that the B7-1 costimulatory molecule is superior to the B7-2 molecule in its capacity to protect against wild-type tumor c hallenge and eradicate minimal residual disease. These results provide compelling evidence that the B7-1 and B7-2 costimulatory signals are functionally distinct, thus resulting in clinically significant differ ences in the induction of antitumor immunity in vivo.