A NEW CANCER-ASSOCIATED ANTIGEN DEFINED BY A MONOCLONAL-ANTIBODY AGAINST A SYNTHETIC CARBOHYDRATE CHAIN

Carbohydrate antigens can be designed by referring to previously defined carbohydrate structures. We have generated a novel monoclonal antibody (MAb) (Fl alpha-75) against an artificially designed antigen (Fl alpha), using organic-synthetic chemistry methods and hybridoma technology. Fl alpha (Gal beta l --> 4GlcNAc beta l --> 6GalNAc alpha l --> Ser/Thr) belongs to core type 6 of O-linked glycans, which has not been previously reported in human cancers. To produce antibodies against Fl alpha, a glycolipid was synthesized which carries the carbohydrate portion of Fl alpha on a ceramide foundation (Gal beta l --> 4GlcNAc beta l --> 6GalNAc alpha l --> Cer). The MAbs we obtained (Fl alpha-75, Fl alpha-87) specifically recognized Fl alpha and had only a very weak or no cross-reactivity with other glycolipids similar to Fl alpha. We investigated the expression of Fl alpha in human tissues, including 110 gastric cancers, 73 colon cancers and 42 pancreatic cancers. Fl alpha was found in human cancerous tissues but not in normal adult tissues. The rate of positive staining with Fl alpha-75 was 80% for gastric cancer, 52.4% for pancreatic cancer and 38.4% for colon cancer. Fl alpha-75 reacted with the pyloric glands of the stomach, the centro-acinar cells of the pancreas, the convoluted tubules of the kidney and the terminal bronchioles of the lung. (C) 1994 Wiley Liss, Inc.