ROLE OF B7-1 IN MEDIATING AN IMMUNE-RESPONSE TO MYELOID-LEUKEMIA CELLS

A costimulatory signal from B7-1 (CD80) to its counter-receptor CD28 i s required for T-cell activation. Many tumors, including most human le ukemias, lack expression of B7-1, and this has been suggested to contr ibute to the failure of immune recognition of these diseases. A murine leukemia model system was developed to assess the potential role of B 7-1 in the induction immunity to leukemia cells. The nonleukemic 32Dc1 3 myeloid cell line was transformed by transfection of the BCR/ABL gen e, generating a subline (32Dp210/clone 26) that was leukemic and rapid ly lethal to syngeneic, immunocompetent C3H/HeJ mice or T-cell-deficie nt nude mice. B7-1-modified leukemic cells remained lethal in nude mic e, but caused only a transient, nonlethal leukemia in C3H/HeJ mice. Af ter a single exposure to live, nonirradiated B7-1-modified leukemic ce lls, C3H/HeJ mice developed protective immunity against subsequent cha llenge with B7-1(-) leukemic cells. Further, hyperimmunization with B7 -1(+) leukemic cells prolonged the survival of mice previously injecte d with a lethal number of B7-1(-) leukemic cells. These results indica te that myeloid leukemic cells may be attractive candidates for B7-1 g ene transfer. (C) 1995 by The American Society of Hematology.