""""""""Tumor associated monoclonal antibodies (mAb) are potential therapeutic agents as selective carriers of cytotoxic agents to malignant cells. This hypothesis is tested in animal model systems with mAbs directed toward 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 I-131, 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 physical characteristics of emission. Research continues to focus on expanding clinical use of Y-90 and on completing pre-clinical studies with the alpha-particle emitting radionuclides Bi-212, Bi-213, and At-211. The ongoing clinical trials at the NIH currently employ the second generation bifunctional chelating agent 1B4M-DTPA (aka MX-DTPA) for sequestering Y-90. Recent results in chelate design technology have revealed an in vivo dependency of the absolute configuration of the bifunctional chelating agent to optimize radio-metal complex stability. Due to these results, all current efforts involving In-111, lanthanide ions, and Bi-212,213 have been converted to being performed with CHX-A'' DTPA. Future clinical trials, such as those being planned with mAb 7G7 in conjunction with humanized anti-Tac for the treatment of ATL, would then employ this ligand. Additionally, preliminary efforts toward bringing At-211 into clinical use have proven positive with the development of new linkers based upon trialkyl-stannyl chemistry for electrophilic displacement by At-211 and radiolabeling humanized anti-Tac treating At as a halogen.""""""""
Showing the most recent 10 out of 66 publications
