The goal of Project I is to evaluate the use of radiolabeled anti- idiotype antibody for treating patients with progressive B cell lymphomas. This approach is based on our studies demonstrating that radiolabeled antibodies reactive with murine lymphoma cells are significantly more effective than unlabeled antibodies in inducing tumor regression, our previous demonstration that anti- idiotype antibodies can localize to tumors, and preliminary data showing that I-131-labeled anti-idiotype antibodies can deliver greater radiation to tumor than normal tissues in patients with B cell lymphoma. We specifically intend to examine the pharmacokinetics and radiation dosimetry of I-131-labeled anti- idiotype antibodies. In patients in whom tumor would receive greater radiation than critical normal organs, including marrow, we will then evaluate the therapeutic efficacy and toxic effects of the radiolabeled anti-idiotype antibodies. Patients in whom significant hematologic toxicity occurs will receive an infusion of stored autologous marrow treated to deplete lymphoma cells. Future studies will be aimed at improving the biodistribution of radiolabeled antibodies and may include evaluating antibody F(ab')2 and Fab fragments, and testing alternative infusion schedules. The use of other labeling methods or other radiolabels will be considered.
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