The goal of the proposed studies is to improve the therapeutic effectiveness of monoclonal antibodies in the treatment of lymphoma. Our previous studies using unmodified antibodies against a normal T cell differentiation antigen to treat murine T cell lymphoma demonstrated anti-tumor activity. However, limitations of this approach suggested the use of antibodies conjugated with a radionuclide to improve therapeutic effectiveness. Preliminary studies using I-131-labeled monoclonal anti-Thy 1.1 antibodies have met with success in eliminating large tumor masses. We now propose to evaluate ways to improve the effectiveness of this approach by increasing the amount of radiation that can be targeted to a solid tumor mass as compared to critical normal organs. We will determine whether localization of radiolabeled antibody at tumor sites can be improved by using IL-2 to increase antibody uptake. We will also determine whether the maximum radiation dose that can be delivered to tumor can be increased by using radioprotectors to reduce radiation toxicity to normal organs and whether the biodistribution of the antibody targeted radionuclide can be improved by utilizing a new iodination method. The methods developed in these studies with large tumor masses will then be applied in efforts to eliminate disseminated transplanted and spontaneous lymphoma. In these studies, the effectiveness of antibodies specific for malignant as compared to normal T cells will be assessed. The success of these techniques in improving the therapeutic efficacy of radiolabeled monoclonal antibodies in this murine model would provide the basis for the use of these new approaches in clinical trials with patients with lymphoma.
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