The main focus of the Targeted Therapy clinic continues to be the development of new therapeutic agents for solid tumor using monoclonal antibodies. Working with Dr. Ira Pastan, DBS, NCI, we developed recombinant immunotoxins and radiolabeled antibodies that are being tested in the Medicine Branch. Currently, we are conducting three phase I trials and performing correlative laboratory studies stemmed from these research efforts. These agents (immunotoxin LMB-1, single-chain recombinant immunotoxin LMB-7 and In111 and Y90 radiolabeled mAb B3) target adult patients with advanced solid tumors such as breast, gastrointestinal, ovarian, lung and bladder carcinomas. The evidence of anti-tumor activity in breast and colon cancer patients treated with immunotoxin LMB-1 is very encouraging. We also plan to initiate a pilot study using LMB-1 for breast cancer patients post-autologous bone marrow transplant to target a population with minimal disease. Concurrent use of immunotoxin with immunosupressive agents to decrease immunogenicity are also being planned. Discovery and development efforts in the Laboratory of Molecular Biology, DBS, NCI have produced new generation recombinant immunotoxins that will be available for clinical trials in near future. One of these is e23(dsFv) - PE38, an immunotoxin targeting tumors that express the erb-2 antigen. It is presently undergoing pre-clinical primate testing. Another agent, B3(dsFv)-PE38, is a single-chain disulfide recombinant molecule that is much more stable than LMB-7 and should have better distribution in tumors according to preliminary laboratory data.
