Biosynthesis and Expression of the Disialoganglioside G_D2, a Relevant Target Antigen on Small Cell Lung Carcinoma for Monoclonal Antibody-mediated Cytolysis

Monoclonal antibodies (MAbs) 126 (immunoglobulin M) and 14.18 (immunoglobulin G3) react strongly with the cell surface of small cell carcinoma of the lungs (SCCL) and are unreactive with most normal tissues and other neoplasms with the notable exception of tumors derived from cells of neural crest origin. These MAbs react specifically with the oligosaccharide portion of the disialoganglioside G Analysis of total gangliosides from cultured cell lines derived from SCCLindicates that g d2is a predominant ganglioside. A comparison of the reactivities of MAbs against G with those directed against gangliosides G and gd3 each differing from G by a single sugar residue, clearly indicates that is preferentiallyexpressed by cultured cells derived from SCCL. Membranes isolated from these cells exhibit synthetase activity which specifically converts theprecursor to in the presence of uridine diphosphate-N-acetyl galactosamine as the glycosyl donor. We present evidence that in SCCL serves as a relevant target antigen for monoclonal antibody-mediated cytolysis. Specifically, we demonstratethat MAb 14.18 (immunoglobulin G3), can lyse small cell carcinoma of the lung targets by either complement- or antibody-dependent cellular cytotoxicity.