The overall purpose of this project is to investigate and develop a novel vaccine for Acute Myelogenous Leukemia. This product, cationic lipid-DNA complexes (CLDC), is effective via multiple administration routes in broadly stimulating the innate and adaptive immune system and serving as a potent biologic adjuvant. Previous in vitro and in vivo studies suggest that immunization with CLDC plus antigen (CLDC/Ag) may prove to be an effective therapeutic approach in the AML patient, including preliminary data collected by the collaborator on this proposal. Although 70% of AML patients will enter remission after chemotherapy, 60-80% of these patients will relapse and die of their disease. Thus, many current therapeutic approaches to AML are directed at controlling minimal residual disease states achieved after initial chemotherapy. The specific goals of the current project are to optimize route of delivery, confirm normal hematopoesis in vaccinated mice, evaluate protection and identify specific cell types that confer protection, and determine kinetics of tumor growth in therapeutic scenarios using tumor cell lines with varying malignancies. The kinetics of tumor growth will be monitored by flow cytometry of 32D leukemic cells that are stable GFP transfectants. The proposed experiments will generate feasibility data that will be a stimulus for establishing the utility of this novel approach for leukemia immunotherapy in humans. The studies will also provide a direct comparison of the immunomodulatory and vaccine approach as a potential therapeutic intervention utilizing CLDC/Ag. Given the poor overall survival rates of AML patients, it is believed that this approach offers a unique opportunity as an adjunctive therapy to traditional approaches to control minimal residual disease and prevent or delay relapse. ? ? ?
