Immunotherapy of cancer with antibody in experimental animals and in human patients has been a focus of intense interest and investigation for many decades. Our long-term goal is to understand the mechanisms of antibody-dependent destruction of target cells and apply this knowledge in the treatment of neoplastic disorders, particularly acute myelocytic leukemia (AML). We have evaluated the feasibility of antibody therapy in the eradication of a small number of residual AML cells in leukemic rats receiving intensive chemotherapy followed by bone marrow transplantation simulating human AML patients. We used a monoclonal antibody that reacted with both rat and human AML cells so that the effects of the antibody on AML cells and hematopoietic progenitor cells could be tested in rats before this antibody or other cross-reactive antibodies are considered for clinical use. In this proposal, we plan to produce multiple cross-reactive monoclonal antibodies of IgM and IgG isotypes, and evaluate their ability to suppress AML in rats without affecting bone marrow hematopoietic progenitor cells. The antigens recognized by these antibodies will be characterized and normal cells expressing the antigens will be identified. The in vitro activity of these antibodies to suppress human AML cells without affecting human bone marrow cells will be assessed. We will attempt to potentiate the antibody-dependent AML suppression by replacing or non-specifically activating effector cells capable of destroying antibody-sensitized AML cells. We believe that cross-reactive monoclonal antibody therapy will be useful for eradicating minimal residual leukemia cells and add much to the treatment of AML.
