A Novel Antibody Therapeutic for Multiple Myeloma

DESCRIPTION (provided by applicant): Multiple myeloma is an incurable monoclonal proliferative disorder of malignant plasma cells affecting more than 14,000 persons in the U.S.A. per year. Conventional therapies and/or bone marrow transplantation only impr ove survival time with a median of 30-36 months. The goal of Chimeric Technologies, Inc. is to develop an anti-TfR IgA alone or incombination with an FDA approved iron-chelator as a therapeutic to administer systemically to treat multiple myeloma. The goal in Phase I/SBIR was to produce mouse-human chimeric anti-human transferrin receptor (hTfR) dimeric IgA that can be used as a novel and effective anti-proliferative/apoptosis-inducing drug for the treatment of human multiple myeloma. In phase I/SBIR the sp ecific aims were to produce transfectants secreting anti-hTfR dimeric IgA, to purify the anti-hTfR dimeric IgA proteins and to determine the ability of the anti-hTfR IgA to inhibit proliferation of and induces apoptosis in model multiple myeloma cell lines . Having successfully established the proof of principle during the Phase I/SBIR, the goal of Phase II/SBIR studies is to determine the efficacy of the anti-hTfR IgA against primary cells obtained from multiple myeloma patients and in an animal model. To a chieve this goal, the following specific aims are proposed. First, to determine the effect of anti-hTfR IgA on both cell proliferation and apoptosis of primary cells obtained from multiple myeloma patients. Second, to evaluate the additive/synergistic effe ct of the combination of anti-hTfR IgA and the iron-chelating agent deferoxamine (DFO) in model multiple myeloma cell lines. Finally, to determine the in vivo anti-tumor activity of anti-hTfR IgA in SCID mice bearing human plasma cell tumors. The utility o f this therapeutic will not be restricted to the elimination of myeloma cells in vivo, but can also be used for in vitro purging of myeloma cells during ex vivo expansion of hematopoietic progenitor-cells for use in autologous transplantation in multiple m yeloma patients. Similar approach can be applied to other hematopoietic malignancies such as leukemias and lymphomas. Finally, the proposed theapeutic may not necessarily be a replacement for the conventional therapies, but instead would provide an alterna tive therapy to be used in combination with other anti-cancer approaches. PUBLIC HEALTH RELEVANCE: Multiple myeloma is an incurable monoclonal proliferative disorder of malignant plasma cells affecting more than 14,000 persons in the U.S.A. per year. Conve ntional therapies and/or bone marrow transplantation only improve survival time with a median of 30-36 months. Chimeric Technologies, Inc. developed an antibody that is toxic to multiple myeloma cells in a test tube. The goal of Chimeric Technologies, Inc. is to test this antibody alone or in combination with other approved agents as a therapeutic regimen in animals and in clinical trials to administer systemically to treat multiple myeloma and leukemias and lymphomas in patients.