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Biosynthesis and Expression of the Disialoganglioside G_D2, a Relevant Target Antigen on Small Cell Lung Carcinoma for Monoclonal Antibody-mediated Cytolysis¹

Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, California

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_D2. Analysis of total gangliosides from cultured cell lines derived from SCCL indicates that G_D2 is a predominant ganglioside. A comparison of the reactivities of MAbs against G_D2 with those directed against gangliosides G_M2 and G_D3, each differing from G_D2 by a single sugar residue, clearly indicates that G_D2 is preferentially expressed by cultured cells derived from SCCL. Membranes isolated from these cells exhibit G_D2 synthetase activity which specifically converts the precursor G_D3 to G_D2 in the presence of uridine diphosphate-N-acetyl galactosamine as the glycosyl donor. We present evidence that in SCCL, G_D2 serves as a relevant target antigen for monoclonal antibody-mediated cytolysis. Specifically, we demonstrate that MAb 14.18 (immunoglobulin G3), can lyse small cell carcinoma of the lung targets by either complement- or antibody-dependent cellular cytotoxicity.

¹ These studies were supported by grant CA 28420 from NIH. This is Scripps Clinic Publication 4396-Imm.

² Supported by a J. Ernest Ayre junior faculty award from the National Cancer Cytology Center. To whom requests for reprints should be addressed.

Received 4/25/86. Revised 7/11/86. Accepted 7/14/86.

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