The goal of this proposed study is to develop improved bone marrow transplant regimens for the treatment of spontaneous malignant lymphoma in dogs, a model system of transplantation for hematologic malignancies in man. Lymphoma can be permanently eradicated in 25% of animals by treatment with 8.4 Gy total body irradiation (TBI) and autologous marrow transplantation. The disease recurs in the remaining 75% of animals because in some animals the TBI is incapable of eradicating the tumor while in others tumor cells may be reinfused with the remission marrow. In this proposal, the use of monoclonal antibodies as carriers for radioisotopes will be explored with the goal of achieving more directed radiotherapy thereby increasing tumor cell kill in the host without increasing toxicity. Specific experiments will determine the biodistribution and therefore the internal radiation dosimetry associated with the use of an anti-Ia and an anti-T cell antibody. Methods designed to promote localization of antibody in tumor-bearing areas and prevent localization at sites of potential toxicity will be explored. The maximum dose of radiolabeled antibody tolerable with bone marrow support will be defined. The antitumor activity of a treatment regimen composed of radiation delivered by antibody carriers followed by marrow transplantation will be determined in dogs with spontaneous malignant lymphoma. In an effort to reduce the relapse rate following autologous transplantation due to tumor contamination of marrow, methods of removing tumor cells from marrow with in vitro chemotherapy or in vitro treatment with tumor-associated antibodies and complement will be studied.
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