MONOCLONAL ANTIBODIES/SMALL CELL CARCINOMA OF THE LUNG

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This project is designed to explore the diagnostic and therapeutic potential of a panel of monoclonal antibodies (MoAbs) that react with SCCL-associated or specific cell surface antigens. The majority of the MoAbs were prepared in this laboratory during the first years of this on-going study (now in its 4th year) and in addition, we have acquired two SCCL-reactive MoAbs, TFS-2 and TFS- 4 that augment our ability to carry out the studies we propose. In particular, we will undertake a prospective evaluation of SCCL tumor immunophenotyping for the purpose of establishing meaningful clinical correlations. All patients with lung cancer seen at the DHMC will have their tumor cells examined by immunohistochemistry for the expression of antigens defined by a battery of MoAbs. The tumor registry of DHMC will collect the clinical data thus permitting data analyses and correlations. A second project will be the development of a sensitive test for the detection of small numbers of SCCL cells in other cell populations, such as bone marrow. This will involve the use of multiparameter flow cytometry to measure simultaneously DNA content and surface expression of SCCL 175. This technique will be used to establish the incidence of bone marrow metastases and to monitor the efficacy of SCCL purging of bone marrow for autologous bone marrow transplantation (ABMT). Another project will examine the potential of MoAbs to remove SCCL cells from bone marrow using immunomagnetic beads. We will explore the use of several MoAbs conjugated to magnetic microspheres for their abilities, alone and in combination, to prepare marrow from SCCL patients tumor-free for ABMT. Finally, we will prepare hetero-antibodies (HA) of anti-SCCL MoAbs and MoAbs to cytotoxic effector cells. These HA will be examined for their abilities to mediate SCCL killing. We expect these pre-clinical studies to lead immediately to clinical applications for the diagnosis and treatment of patients.