Gene transfer of GM-CSF, CD80 and CD154 cDNA enhances survival in a murinemodel of acute leukemia with persistence of a minimal residual disease

Gene transfer of various cytokines and co-stimulatory molecules has been re ported to induce a potent antileukemic immunity in murine models, however, the relative efficiency and possible synergistic effects between candidate genes have not been extensively investigated We analyzed in a murine model of BCR/ABL acute leukemia whether gene transfer of CD154, CD80 or GM-CSF as a single agent or combination of CD154 + GM-CSF, CD80 + CD154 and GMCSF CD80 in leukemic cells could enhance survival. We observed that CD154 gene transfer induced a marked inhibition of leukemogenicity, and also that CD15 4 and combination of GM-CSF and CD80 gene transfer protected mice against s ubsequent challenge with leukemic cells and had a therapeutic effect for a pre-established leukemia disease. We also found minimal residual leukemic d isease by RT-PCR for 6 to 12 months in 0 to 25% of animals injected with tr ansduced leukemic cells and surviving the challenge without evidence of dis ease, except in the control empty plasmid group where very few mice survive d the challenge but all of those were positive by RT-PCR. These findings su ggest that leukemic cell vaccination by gene transfer can induce a tumor do rmancy phenomenon compatible with long-term survival.