The production of monoclonal antibodies to human tumor-associated antigens holds considerable promise for the development of new diagnostic and therapeutic strategies. To date, very little has been done with soft tissue sarcomas, a diverse group of mesenchymal tumors. We have recently produced several mouse monoclonal antibodies which recognize membrane antigens preferentially expressed on human soft tissue sarcomas. Because our Division of Surgical Oncology sees a large number of patients with this relatively rare form of cancer, we are one of only a small number of research groups capable of conducting an extensive analysis of sarcoma-associated antigens.
The specific aims of this research are: (1) production of a library of mouse monoclonal antibodies directed against tumor-associated membrane antigens of soft tissue sarcomas. Antibodies will be screened by radioimmunoassay for reactivity with plasma membranes prepared from fresh tumor and normal adult tissues. This innovative approach selects for antibodies with diagnostic and therapeutic potential, rapidly addresses questions of in vivo antigen specificity, and avoids antigen artifacts due to cell culture; (2) identification of antigen-bearing cells in histologic sections and localization of antigen expression. Reactive cells in intact tissues will be identified by an immunoperoxidase technique, providing further information on in vivo antigen specificity; (3) use of the antibody library as an aid in the classification of the different histologic types of soft tissue sarcoma. At present, the pathologic classification of sarcomas, important in staging and designing therapy, is often controversial; (4) development of immunoassays for the detection and quantitation of shed antigens in serum and urine of tumor-bearing patients. The results will be analyzed in terms of diagnosis, tumor burden, surgery, and recurrence; and (5) biochemical characterization of identified antigens for protein, carbohydrate, and lipid composition, and comparison to known antigens. Our long-term goals include the clinical use of the antibody library in diagnosis, prognosis, monitoring therapy and recurrence, tumor imaging, and immunotherapy. (2)
