Diagnostic and therapeutic applications of monoclonal antibodies to small cell carcinoma of the lung.

For diagnosis and treatment of small cell lung cancer (SCLC), we have developed two different types of monoclonal antibodies, one of which is useful for specific diagnosis of SCLC. The other has been used for purging tumor cell infiltrates from bone marrow in high-dose chemotherapy followed by autologous bone marrow rescue. The monoclonal antibody, TFS-4, is highly specific for SCLC. It reacts with SCLC but is unreactive with squamous cell carcinoma or adenocarcinoma of the lung. It can distinguish SCLC from non-SCLC in histologic diagnosis at transbronchial biopsy, and in cytological identification of tumor cells in malignant effusions and in infiltrated bone marrow. Radiolabeled TFS-4 specifically accumulated into SCLC tumors and depicted a clear-demarcated tumor image with a gamma scintillation camera. The TFS-4 labeled with 131I inhibited the growth of SCLC tumors transplanted into nude mice. TFS-2 antibody demonstrated "pancarcinoma" reactivity, showing binding to SCLC, non-SCLC, and carcinomas derived from other organs such as the colon, pancreas, and stomach. This antibody failed to react with a variety of normal tissues including lung, bone marrow, spleen, stomach, colon, and pancreas. TFS-2 showed complement-mediated cytolysis of target cells. TFS-2 did not inhibit the growth of hemopoietic progenitors committed to granulocyte-macrophage, or erythroid lineage. In mixed cell populations of tumor cells and bone marrow cells, the antibody effectively killed the tumor cells.