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First Establishment of a Human Monoclonal Antibody Directed to Sulfated Glycosphingolipids S_M4s-Gal and S_M4g, from a Patient with Lung Cancer

Department of Thoracic Surgery, Kitano Hospital, Tazuke Kofukai Medical Research Institute, 13-3, Kamiyamacho, Kitaku, Osaka [M. M., T. T.], and Department of Clinical Science and Laboratory Medicine [R. K.], and Thoracic Surgery, Chest Disease Research Institute [S. H.], University of Kyoto, Kyoto, Japan

Several human monoclonal antibodies directed to tumor-associated glycolipid antigens have been established, but more than one-half of them react with gangliosides and the others react with neutral glycolipids. We report here the first establishment of a human IgM monoclonal antibody directed to the sulfated glycolipid. This monoclonal antibody, M14-376, did not react with S_M3 and S_B1a which have a terminal HSO₃3Galß1R₁, but with the simple sulfolipids S_M4s-Gal and S_M4g which contain a terminal HSO₃3Galß1-OCH₂R₂; however, lyso-S_M4s-Gal and lyso-S_M4g did not bind M14-376. These results suggest that terminal HSO₃3Gal and part of the hydrophobic region of the glycolipid are recognized by M14-376. Directly biotinylated M14-376 was used for immunohistochemical staining of 140 formalin-fixed, paraffin-embedded lung cancer tissue sections to study the distribution of the antigen. A high incidence of positive staining was found in adenocarcinoma (39.5%, 17 of 43), followed by large cell carcinoma (20.0%, 5 of 25), while this antigen was rarely detected in small cell carcinoma (4.7%, 1 of 21) and squamous cell carcinoma (3.9%, 2 of 51). Thin layer chromatography immunostaining of glycolipids extracted from lung cancer tissues showed the presence of only S_M4s-Gal in adenocarcinoma, but S_M4g was not found in any subtype of lung cancer. Immunohistochemical staining revealed that this antigen was expressed in normal kidney, testis, and brain, but erythrocytes, granulocytes, and lymphocytes were negative in cytofluorometric analysis.

¹ This study is supported in part by the Japanese Lung Cancer Society Award to M. M. To whom requests for reprints should be addressed.

Received 10/21/91. Accepted 2/10/92.

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