MONOCLONAL-ANTIBODY DIRECTED AGAINST COLON-CANCER MUCIN HAS HIGH SPECIFICITY FOR MALIGNANCY

Exposure of core carbohydrate structures such as NeuAc alpha2-6GalNAc- Ser/Thr (sialosyl-Tn) in mucus glycoproteins is often associated with malignant transformation in a number of different tissues. Reagents th at specifically identify such structures would be useful in the diagno sis of cancer. Monoclonal antibody JT10e has been produced against muc ins from xenografts of LS174T colon cancer cells but also reacts with mucins of pancreatic cancer xenografts. The following data suggest tha t JT10e reacts with sialosyl-Tn: (1) reactivity with bovine and ovine submaxillary mucins; (2) reactivity sensitive to neuraminidase or mild acid; (3) inhibition of reactivity by NeuAc and NeuAc alpha2-6 lactos e; and (4) lack of reactivity with other glycoproteins with related ca rbohydrate structures but no sialosyl-Tn. JT10e is distinguishable fro m 2 other antibodies which react with sialosyl-Tn, B72.3 and TKH2 beca use JT10e: (a) did not react with normal gastric tissue while B72.3 an d TKH2 did; (b) was only partially inhibited by TKH2 and not at all by B72.3; (c) did not react with Tn antigen while B72.3 did; and (d) bou nd more strongly to pancreatic cancer mucins than did either B72.3 or TKH2. JT10e reacted with a high percentage of malignant colonic, pancr eatic, gastric and mammary tissues but not with the corresponding norm al tissues. A high percentage of patients with colonic, pancreatic, ga stric, mammary and lung cancers had elevated blood levels of JT10e ant igen. A number of colonic cancer patients had elevated JT10e antigen l evels without corresponding elevations in CA19-9 levels. These results suggest that JT10e antibody could be used in conjunction with other m ucin markers to improve the identification of malignancy in colon, and to study the structure of oligosaccharides in cancer mucins.