Protective and therapeutic immunity against leukemia induced by irradiated B7-1 (CD80)-transduced leukemic cells.
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.
Hirano
N
N
Third Department of Internal Medicine, University of Tokyo.
Takahashi
T
T
Takahashi
T
T
Azuma
M
M
Yazaki
Y
Y
Yagita
H
H
Hirai
H
H
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015316:Genetic Therapy; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000628:therapy*; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D015996:Survival Rate; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014162:Transfection / Q000379:methods
D018122:B7-1 Antigen; D015395:Histocompatibility Antigens Class I; D018799:Intercellular Adhesion Molecule-1