Tumor associated monoclonal antibodies (mAb) are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. We are testing this hypothesis in animal model systems with mAbs directed towards antigens associated with a variety of malignancies. The cytocidal agents being employed are various radionuclides. Their relative efficacy when conjugated to monoclonal antibodies is assayed and compared to that of monoclonal antibodies alone, radiolabeled with 131I, or conjugated to toxins. The several radionuclides chosen for study span the range of radionuclidic properties available thereby assaying the effects of energy of emission, half-life, and characteristic of emission. Recent research continues to focus on the clinical use of 90Y and on completing preclinical studies with the alpha-particle emitting radionuclides 212Bi and 213Bi. Most recently the Hot Cell that we had installed in the radiation laboratory in order to prepare high level activity (>10 mCi) doses of antibodies labeled with 212Bi. Studies of toxicity and efficacy in a heart transplant rejection suppression model has been completed in monkeys. Complementary therapy experiments in murine models continue to define the parameters for support of an IND for the treatment of leukemia patients. Studies like these are providing for human medicine a basis for design of rational therapies of malignancies by selectively targeting cytocidal agents to tumors, as well as metastases and will promote improved diagnostic imaging of malignancies.
Showing the most recent 10 out of 66 publications
