Protective and Therapeutic Immunity Against Leukemia Induced by Irradiated B7-1 (CD80)-Transduced Leukemic Cells

Abstract

B7 molecules provide an important costimulatory signal for T cell receptor/CD3-mediated T cell activation via binding to their cognate receptors, CD28 and CTLA-4. We have introduced B7-1 (CD80) into M1 cells, spontaneously-occurred mouse myelocytic leukemic cells and assessed its potential in the induction immunity to leukemia cells. Syngeneic, immunocompetent SL mice receiving polyclonal B7-1-transduced M1 cells showed prolonged survival than control mice. Two independent B7-1-transduced monoclonal sublines, M1-B7-1+ (F20) and M1-B7-1+ (F7), were rejected in 100% an 50% of SL mice, respectively. In vivo depletion of T cell subsets showed that both CD4+ and CD8+ T cells were indispensable for the B7-1-dependent anti-leukemic immunity. Although a single exposure to irradiated monoclonal M1-B7-1+ cells were not fully effective, multiple exposures induced protective immunity against subsequent challenge with M1 cells. Furthermore, hyperimmunization with irradiated monoclonal M1-B7-1+ (F7) cells could partly cure mice previously injected with a lethal number of M1 cells. Although other groups have demonstrated that live, proliferating B7-1-transduced leukemic cells can improve antitumor immunity, this is the first report which shows that irradiated B7-1-transduced myeloid leukemic cells can induce protective and therapeutic immunity against leukemia.