The overall objective of this program project is the assessment of the role of monoclonal antibodies (MAbs) in the diagnosis, detection, and therapy of cancer. this group has generated MAbs against gastrointestinal tumors, particularly colorectal and pancreatic carcinomas, and has demonstrated their use in diagnosis, detection and therapy. The project addresses important preclinical (model) and clinical questions on the prospects and limitations of these relatively specific agents for gastrointestinal cancers, particularly from a comparative view and involving the testing of certain basic questions regarding the proper clinical use of such MAbs. It has been found that development of specific and sensitive immunoassays to detect and quantitate circulating shed tumor antigen can prove useful for early detection and diagnosis that can alter patient management. In vivo localization of tumor with radiolabeled antibody can serve as a staging and management tool. Additionally, evidence is mounting that tumoricidal agents can be made more effective when specifically targeted to the tumor site by virtue of conjugation to antibody. A complementary and very promising approach towards treatment of cancer is the use of monoclonal anti-idiotype antibodies as vaccines for the development of specific, active immunity in the cancer patient. The proposed program project is organized as a biological response modifier study, involving four closely interrelated basic laboratory and clinical research projects that will focus on the management of cancer with monoclonal antibodies. The basic laboratory studies will assess the role of several new monoclonal antibodies and their diagnostic and therapeutic potential, and point to new strategies for MAb-mediated cancer detection and therapy.
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