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) (Flα-75) against an artificially designed antigen (Flα), using organic-synthetic chemistry methods and hybridoma technology. Flα (GalβI 4GlcNAcβI 6GalNAαI Ser/Thr) belongs to core type 6 of O-linked glycans, which has not been previously reported in human cancers. To produce antibodies against Flα, a glycolipid was synthesized which carries the carbohydrate portion of Flα on a ceramide foundation (GalβI 4GlcNAcβI 6GalNAcαI Cer). The MAbs we obtained (Flα-75, Flα-87) specifically recognized Flα and had only a very weak or no cross-reactivity with other glycolipids similar to Flα. We investigated the expression of Fin in human tissues, including 110 gastric cancers, 73 colon cancers and 42 pancreatic cancers. Flα was found in human cancerous tissues but not in normal adult tissues. The rate of positive staining with Flα-75 was 80.0% for gastric cancer, 52.4% for pancreatic cancer and 38.4% for colon cancer. Flα-75 also reacted with the tissues neighboring gastric and pancreatic tumors but not intensely. Among fetal tissues, Flα-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.