The proposed research is directed toward the continued development of a panel of monoclonal antibodies with specificity for antigens expressed on tumor cells of small cell carcinoma of the lung (SCCL). We have already produced four potentially useful monoclonal antibodies (MoAbs) that are relatively specific for SCCL. These four MoAbs, along with other murine and human MoAbs that we propose to develop, will be utilized to study the immunobiology of SCCL cells and thus to develop the basis for potentiation immunotherapy of this disease in an autologous bone marrow transplantation program. Freshly isolated tumor cells from patients with SCCL and cell lines available at the Dartmouth Medical School will be used in a variety of in vitro studies as well as for the production of additional hybridomas. Reactivities with freshly isolated SCCL tissue as well as cell lines will be assessed by cytofluorography and by complement-dependent cytotoxicity. Cell surface antigens characteristic of SCCL cells will be purified, partially characterized and used for the preparation of a second generation of anti-SCCL MoAbs. Heterogeneity of antigen expression in SCCL within and among individual cell populations from patients, and SCCL cell lines and clones of SCCL cell lines will be evaluated by cytofluorography. Assays for detection of SCCL-associated antigens in body fluids of patients will be developed and used to correlate antigen expression by cell lines and in the serum of patients with SCCL with disease parameters. MoAb induced modulation of cell surface antigens or tumor cell selection will be evaluated as possible tumor cell escape mechanisms. Attempts will be made to develop a panel of MoAbs that is capable of abrogating tumor cell escape. Overall, these studies represent a comprehensive approach to an evaluation of the potential utility of MoAbs in the diagnosis and therapy of SCCL and in basic studies of SCCL cell biology.
