The overall goal of this program is to develop strategies for treating patients with hematologic malignancies by using radiolabeled monoclonal antibodies. Our studies to date have demonstrated the feasibility of treating patients with antibody labeled with relatively high amounts of I- 131 and of overcoming the resulting myelosuppression by marrow transplantation. In a Phase I study of lymphoma, nearly all treated patients achieved a complete response, some of which are enduring now for more than three years in the absence of significant non-hematopoietic toxicity. Consequently, we are proposing to continue to study patients with hematologic malignancies including B-cell lymphomas and acute leukemia. In these projects we will continue to assess the biodistribution and radiation dosimetry of radiolabeled antibodies and treat patients in whom favorable dosimetry is achieved. Specifically, in Project I, we will continue to evaluate radiolabeled antibodies that react with both normal and malignant B-cells for treating patients with lymphoma. These studies will combine targeted radiation with high dose therapy regimens prior to autologous marrow transplantation. In Project II, we will evaluate the use of anti-myeloid monoclonal antibodies in patients with acute leukemia for delivering radiation to tumor and to the bone marrow where this tumor resides. In these studies, radiation delivered by antibody will be in addition to total body irradiation and/or chemotherapy, as part of a preparative regimen prior to marrow transplantation. In Project III we will evaluate if improved delivery of radiation to tumor can be achieved using different antibodies and/or radionuclides. Radioimmunoconjugates selected in preclinical studies will be evaluated in patients using quantitative imaging methods developed in this project.
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