Immunogene therapy against mouse leukemia using B7 molecules.

Abstract

B7 costimulatory molecules play an important role in T-cell activation. It is well known that tumor cells that express B7 molecules can elicit antitumor immunity, but little is known regarding which B7 molecule, B7-1 (CD80) or B7-2 (CD86), can do so more efficiently. To address this issue, we have introduced B7-1 or B7-2 into 8709 cells, a radiation-induced mouse myelocytic leukemic cell line, and have compared their potentials regarding the induction of antitumor immunity. Either B7-1- or B7-2-transduced monoclonal sublines, 8709/B7-1 or 8709/B7-2, respectively, diminished tumorigenicity in syngeneic C3H mice. Some reports have indicated that B7-1 is superior to B7-2 in the induction of antitumor immunity. Contrary to these results, the 8709/B7-2 lines are superior to the 8709/B7-1 lines in their capacity to induce antitumor immunity. In vivo depletion of lymphocyte subsets demonstrated that both CD4+ and CD8+ T cells were indispensable for B7-1- or B7-2-dependent antitumor immunity, whereas natural killer cells were not. These results suggest that in some circumstances, B7-2 molecule is more effective than B7-1 molecule in eliciting antitumor immunity.