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 Philadelphia chromosome-positive acute lymphoblastic leukemia. The immunostimulatory molecules chosen for this study were the cytokines IL-2 and GM-CSF and the costimulatory ligand CD80 (B7.1). We used a murine model based on a BALB/c pre-B cell line, BM185wt, in which leukemia is induced by the p185 BCR-ABL oncogenic product, which reproduces Philadelphia chromosome-positive ALL. BM185wt cells were transduced with retroviral 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 immunocompetent mice, but not in immunodeficient mice, indicating an immune response against the modified leukemia cells. Expression of CD80 caused leukemia rejection in 50% of the cohort, which was associated with the CD4+ and CD8+ T cell-dependent development of anti-leukemia cytotoxic T lymphocytes. Furthermore, mice surviving the BM185/CD80 challenge or preimmunized with irradiated BM185/CD80 cells developed an immune response against subsequent challenge with the parental leukemia. These studies provide evidence that immunotherapeutic approaches can be developed for the treatment of ALL.
Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA 90027, USA.
R
R
Stripecke
D C
DC
Skelton
T
T
Gruber
D
D
Afar
P K
PK
Pattengale
O N
ON
Witte
D B
DB
Kohn
D000276:Adjuvants, Immunologic / Q000235:genetics; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics*; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID / Q000276:immunology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000401:mortality; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology* / Q000628:therapy; D014161:Transduction, Genetic / Q000235:genetics; D014407:Tumor Cells, Cultured; D014612:Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D018122:B7-1 Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; D007376:Interleukin-2; D014612:Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor