Monoclonal Antibodies for Diagnosis and Potential Therapy of Small Cell Lung Cancer—The Ganglioside Antigen Fucosyl-Gm1

Abstract

Lung carcinomas represent a highly heterogenous group of tumors, which includes small cell lung cancer (SCLC). The ganglioside fucosyl-GM₁ (FucGM₁) was originally identified as a highly selective marker for SCLC. A number of monoclonal antibodies against FucGM₁ have been produced against the purified ganglioside, and their specificity validated. With monoclonal antibodies, FucGM₁ has been detected in tissues as well as in serum samples from SCLC patients. A sensitive, quantitative assay method for FucGM₁ was developed based on scintillation proximity immunoassay (SPA): A specific monoclonal antibody against FucGM₁ is bound to immunosorbent particles that contain a fluor. When radiolabelled FucGM₁ binds to these particles, the fluor is excited, and the photons emitted can be measured directly in a β-counter. This sensitive assay for FucGM₁ has several potential diagnostic applications: differential diagnosis of SCLC, development of serum assays for diagnosis and monitoring of disease progression, and monitoring of patient response to therapy. The expression of FucGM₁ in SCLC cells is heterogeneous, and may depend on the differentiated state of tumor cells. However, monoclonal antibodies specific for FucGM₁ may have important future applications for radioimmunoimaging as well as in immunotherapy for SCLC.