Development of new immunogene therapy for refractory leukemia and lymphoma

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We have treated 3 renal cancer patients using granulocyte macrophage colony stimulating factor (GM-CSF) gene-transduced autologous renal cancer cells as clinical trials. To develop more efficient immunogene therapy for malignacy in future, we have been trying to determine the most powerful effector molecules functioning in rejecting leukemia cells from normal immune mice. Our previous observation demonstrated that GM-CSF transduced WEHI3B, mouse leukemia cells induced strong antitumor immunity in Balb/c mice, on the other hand, wild WEHI3B cells made tumor in Balb/c mice and nude mice. Using SAGE (sequence analysis of gene expression) method, we screened 30,000 mRNA fragments, tag sequences, which speciflically expressed at the sites of WEHI3B cells injected to Balb/c or nude mice as well as WEHI3B/GM-CSF cells injected to Balb/c mice. 9 candidate fragments, which were specifically expressed in WEHI3B cells rejection system, were obtained in this study and precise analysis has been under way to characterize these newly identified genes from the standpoint of immunogene therapy for malignancies.