VACCINE EFFECT OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR ORCD80 GENE-TRANSDUCED MURINE HEMATOPOIETIC TUMOR-CELLS AND THEIR COOPERATIVE ENHANCEMENT OF ANTITUMOR IMMUNITY

To develop immunogene therapy targeting minimal residual hematopoietic tumor cells in patients, we transduced murine GM-CSF or CD80 gene int o murine WEHI 3B myelomonocytic leukemia and EL-4 thymic lymphoma I ce lls using retroviral vectors and evaluated their effects on inducing a ntitumor responses in syngeneic host mice. Subcutaneously injected GM- CSF- and CD80 gene-transduced WEHI 3B (GMCSF/WEHI/3.2 or CD80/WEHI/1.8 , respectively) cells lost their original tumorigenicity in immunocomp etent syngeneic mice. Results from tumor inoculation experiments using athymic nude mice suggested that the rejection of GMCSF/WEHI/3.2 in i mmunocompetent mice depended fully on T cells and that of CD80/WEHI/1. 8 depended partly on T cells and partly on NK cells. In both WEHI 3B a nd EL-4 models, irradiated GM-CSF gene-transduced cells provided stron g immunoprotection against wild-type cells, but irradiated CD80 gene- transduced cells did not. A remarkably high cooperative effect was obt ained when irradiated GMCSF/EL-4 and CD80/EL-4 were inoculated togethe r. These results suggested that the tumor vaccine effect is efficientl y enhanced by GM-CSF gene transduction and CD80 gene transduction indu ces some protective antitumor immunity in co operation with GM-CSF gen e transduction.