Glycosphingolipid tumor antigens.

Abstract

Tumor-associated glycosphingolipids are a common finding in human tumors, and monoclonal antibodies directed to defined carbohydrate epitopes of these structures have been developed. A majority of the glycosphingolipid antigens are of the lacto series, types 1 and 2, and these epitopes are often also found on glycoproteins. The tumor-associated gangliosides of the ganglio series, preferentially found in tumors of neuroectodermal origin, have binding epitopes that have not been detected in glycoproteins. A large number of monoclonal antibodies, mainly murine but some human, have been produced, and their epitope specificity defined. These antibodies have been used for investigation of the role of tumor-associated glycosphingolipids in tumor cells. Some antibodies have been shown to inhibit the growth of tumor cell lines in vitro and in vivo and to influence the adhesion properties of tumor cells, and some antibodies have been shown to give a clinical response. Tumor cell lines are commonly used in tumor biology studies, but the expression of tumor-associated glycosphingolipids in tumor cell lines does not always reflect their expression in the tumor tissue from which the cell line originates. The expression of tumor-associated glycosphingolipids has also been shown to be different in cells grown in vitro or as solid tumors in nude mice or rats. In conclusion, monoclonal antibodies specific for tumor-associated glycosphingolipids may be valuable tools in diagnosis and, in addition, in therapy, glycosphingolipids may also be used in active immunotherapy. The availability of these antibodies also opens the possibility of studying the biological function of glycosphingolipids and may then lead to new approaches for the improved diagnosis and therapy of human tumors.