Tk, a new colon tumor-associated antigen resulting from altered O-glycosylation.

Abstract

Erythrocyte polyagglutination antigens T and Tn are truncated O-glycan chains that are also carcinoma-associated antigens. We investigated whether Tk polyagglutination antigen could similarly be a carcinoma-associated marker and a target of immunotherapy. Monoclonal antibody LM389 was raised against Tk erythrocytes and tested by immunohistochemistry. LM389 strongly reacted with 48% human colorectal carcinomas. Labeling of normal tissues was visible on epithelial cells, mainly digestive, but was confined at a supranuclear level. Expression of the antigen on cloned human carcinoma cells correlated with sialosyl-Tn expression. O-Sialoglycoprotein endopeptidase treatment revealed that on carcinomas and cell lines, the epitope was present on O-glycans. Antibody specificity was determined using synthetic carbohydrates. Direct binding and inhibition studies indicated that LM389 best ligands were terminated by two branched N-acetylglucosamine units. Screening of murine cellular cell lines with LM389 allowed development of an experimental model with Tk-positive and -negative cells in syngeneic BDIX rats. Vaccination of rats with Tk erythrocytes provided a protection against growth of rat Tk-positive, but not of Tk-negative, tumor cells in association with the development of antibodies. Taken together, the results indicate that Tk polyagglutination antigen is a new colorectal carcinoma-associated antigen, absent from the normal cell surface, resulting from alteration of O-glycans biosynthesis and with potential as a target of immunotherapy.

• Authors: M Meichenin, J Rocher, O Galanina, N Bovin, N Nifantev, A Sherman, E Cassagnau, M F Heymann, J Bara, R H Fraser, J Le Pendu
• Journal: Cancer research (Cancer Res) Vol. 60 Issue 19 Pg. 5499-507 (Oct 01 2000) ISSN: 0008-5472 [Print] United States
• PMID: 11034094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, Tumor-Associated, Carbohydrate
• Epitopes
• Polysaccharides
• Glycoside Hydrolases
• keratan-sulfate endo-1,4-beta-galactosidase
• beta-Galactosidase

Topics

• Adenocarcinoma (immunology, metabolism, prevention & control)
• Animals
• Antibodies, Monoclonal (immunology)
• Antibody Specificity
• Antigens, Tumor-Associated, Carbohydrate (biosynthesis, immunology, metabolism)
• Carbohydrate Sequence
• Colorectal Neoplasms (immunology, metabolism, prevention & control)
• Epitopes (immunology)
• Erythrocyte Aggregation (immunology)
• Erythrocytes (immunology)
• Glycoside Hydrolases
• Glycosylation
• Hemagglutination (immunology)
• Humans
• Immunization, Passive
• Immunohistochemistry
• Mice
• Mice, Inbred BALB C
• Molecular Sequence Data
• Polysaccharides (immunology)
• Rats
• Rats, Inbred Strains
• Tumor Cells, Cultured
• beta-Galactosidase (immunology, pharmacology)