Markedly Different Antibody Responses to Immunized Small Cell and Non-Small Cell Lung Cancer Cells

Monoclonal antibodies (MoAbs) to antigens of human small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) were produced from BALB/c mice immunized with either intact cultured cells or membrane preparations from cultured tumor cells. Of 172 MoAbs produced from two NSCLC immunized mice and reactive to NSCLC cells, 137 bound staphylococcal Protein A directly, and only 11 of these 172 MoAbs were significantly reactive with cultured SCLC cells by a solid-phase radioimmunoassay. In contrast, only 16 of 99 MoAbs produced from two SCLC immunized mice and reactive to SCLC cells directly bound Protein A, and most were of an IgM isotype, but 98 of 99 of these antibodies also reacted with cultured NSCLC target plates. Twenty hybridomas producing antibodies reactive with lung cancer cells but not with a B-lymphoblastoid line were cloned. Eleven of these cloned hybridomas were from NSCLC fusions, and nine were from SCLC fusions. When representative hybridoma supernatants were tested against a broad panel of SCLC and NSCLC target plates a similar pattern was seen, with the supernatants from NSCLC-derived hybridomas only reacting strongly to the NSCLC target plates, but the supernatants from SCLC-derived hybridomas always reacting to both SCLC and NSCLC plates. We conclude that the humoral response to immunization with NSCLC cells or membrane preparations is predominantly IgG and that to SCLC is predominantly IgM. Furthermore, many IgG MoAbs reactive with NSCLC lines are poorly reactive with SCLC cells.