The overall goal of this program is to develop strategies for treating patients with hematologic malignancies by using radiolabled monoclonal antibodies. We propose to study patients with hematologic malignancies including B cell lymphomas and acute nonlymphocytic leukemia because of the known radiosensitivity of these tumors. Specifically, in project I we plan to evaluate radiolabeled anti-idiotype antibodies for treating patients with lymphoma. We will compare results obtained with these tumor-specific antibodies with those obtained in project II in which we will use radiolabeled antibodies that react with both normal and malignant B cells to treat a similar group of patients. In project III we will evaluate the use of anti-myeloid monoclonal antibodies in patients with acute nonlymphocytic leukemia for delivering radiation to tumor and to the bone marrow where this tumor resides. In each of these projects we will assess the pharmacokinetics and radiation dosimetry of the I-131-labeled antibodies and treat patients in whom favorable dosimetry is achieved. Initial studies in all three projects will determine the toxicity of a single bolus infusion of I-131-labeled intact antibody. Based on these initial studies we plan phase II clinical trials. We anticipate that significant hematologic radiation toxicity may occur and that this can be overcome by infusing cryopreserved autologous bone marrow cells. Future studies will evaluate strategies that may improve localization to tumor which may include, depending on our initial data, the use of the antibody fragments, alternative infusion schedules and, in projects II and III, antibodies of different specificities.
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