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

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Abstract
B7 molecules provide an important co-stimulatory 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 occurring mouse myelocytic leukemic cells, and assessed its potential to induce antitumor immunity to leukemia cells. Syngeneic, immunocompetent SL mice receiving two independent B7-1-transduced monoclonal sublines, M1-B7-1/F/clone F20 and M1-B7-1/F/clone F7, were rejected in 57% and 43% 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 of irradiated monoclonal M1-B7/1/F cells was not fully effective, multiple exposures induced protective immunity against subsequent challenge with parental M1 cells. Furthermore, multiple vaccinations with irradiated monoclonal M1-B7-1/F/clone F7 cells could cure 67% of mice previously injected with a lethal number of M1 cells. These results emphasize that multiple exposures of irradiated B7-1-transduced myeloid leukemic cells can induce protective and therapeutic immunity against leukemia and that B7-1-mediated gene therapy may have therapeutic efficacy for patients with acute myelocytic leukemia. B7-1 (CD80)-mediated immuno-gene therapy was performed against M1 cells, spontaneously occurring mouse myelocytic leukemic cells. In our system, multiple exposures of irradiated B7-1-transduced M1 cells induced protective immunity in syngeneic mice against subsequent challenge with M1 cells. Furthermore, multiple vaccinations with irradiated B7-1-transduced M1 cells could cure mice with established leukemia.