IMMUNE-RESPONSE TO PHILADELPHIA-CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC-LEUKEMIA INDUCED BY EXPRESSION OF CD80, INTERLEUKIN-2, AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

We examined the potential of generating an immune response against Phi ladelphia chromosome-positive acute lymphoblastic leukemia, The immuno stimulatory molecules chosen for this study were the cytokines IL-2 an d GM-CSF and the costimulatory ligand CD80 (B7.1). We used a murine mo del based on a BALB/c pre-B cell line, BM185wt, in which leukemia is i nduced by the p185 BCR-ABL oncogenic product, which reproduces Philade lphia chromosome-positive ALL, BM185wt cells were transduced with retr oviral vectors and the transduced clones expressing mIL-2, mGM-CSF, or mCD80 were used for challenge. Expression of the immunomodulators by BM185 cells was correlated with delay in leukemia development in immun ocompetent mice, but not in immunodeficient mice, indicating an immune response against the modified leukemia cells. Expression of CD80 caus ed leukemia rejection in 50% of the cohort, which was associated with the CD4(+) and CD8(+) T cell-dependent development of anti-leukemia cy totoxic T lymphocytes. Furthermore, mice surviving the BM185/CD80 chal lenge or preimmunized with irradiated BM185/CD80 cells developed an im mune response against subsequent challenge with the parental leukemia, These studies provide evidence that immunotherapeutic approaches can be developed for the treatment of ALL.