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. It is the second most common hemologic malingnacy and his incidnec coninues to rise, producing significant morbidity in the population. Although conventional therapy of multiple myeloma with oral melphalan and prednisone can effect remissions in approximately 40% of patients, the disease remains incurable, with a median overall survival of only 30 to 36 months. Therefore novel strategies are required for the treatment of multiple myeloma. Based on the observation that anti-TfR fused to avidin that exists in a dimeric form with four antigen binding sites shows anti-proliferative and pro-apoptotic properties, we hypothesize that a dimeric IgA antibody with the same specificity will also target and inhibit the in vitro and in vivo proliferation of multiple myeloma cells by inducing apoptosis. To test this hypothesis we propose the following four specific aims for Phase I. First, to produce transfectants secreting anti-human TfR dimeric IgA. Second, to purify anti-human TfR dimeric IgA protein. Third, to determine the ability of anti-human TfR IgA to inhibit proliferation and induce apoptosis. And fourth, to study the potential toxicity of anti-TfR IgA against normal human hematopoietic stem cells. The results obtained from these studies would not be restricted to multiple myeloma but could also be extended to other hematopoitetic malignancies such as leukemias and lymphomas.
