The goal of these studies are to develop improved methods for detecting and treating malignancies. Our group performs pre-clinical evaluation of antibodies that appear to be promising on initial screening by various laboratories in the NCI and develops these for clinical use. After radiolabeling the antibodies quality control testing is performed by our chemistry staff. They are then administered under the supervision of a Nuclear Medicine Physician and a nurse in the Nuclear Medicine Department Serial blood samples, urine's, and often bone marrow or tumor biopsies are obtained to evaluate the distribution of the MoAb in the body. We have performed pre-clinical studies on murine monoclonal antibody (MoAb) B3 developed in Dr. Ira Pastan's lab. The antibody is labeled using a third generation derivative of DTPA developed in Dr.Otto Gansow's lab and it is labeled with In-111 or Y-90. This antibody is now undergoing testing in a Phase I imaging and therapy trial. Initial imaging studies in 2 patients with colorectal cancer show localization in metastatic lung lesions. This study will continue to accrue patients for imaging and therapy. We are continuing a radioimmunotherapy program in collaboration with Dr. Thomas Waldman's laboratory using In-111 and Y-90 humanized anti- Tac MoAb. The pharmacokinetics of humanized antibody have been characterized and show a longer blood and plasma retention than the murine MoAb. We have documented in vivo complex formation with circulating antigen. Patients have tolerated the injections well. Tumor responses have been observed in 3 patients. Dose limiting toxicity has not been observed with multiple administrations of 5 mCi of Y-90 humanized anti-Tac. The antibody shows good localization and prolonged retention in sites of disease. Although our experience is limited we have not seen significant problems with human anti-human antibody responses. Because of the tumor responses observed thus far with Y-90 humanized anti-Tac this study will continue to accrue patients.
