Tk, a new colon tumor-associated antigen resulting from altered O-glycosylation.
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.
Meichenin
M
M
INSERM U419. Institut de Biologie, Nantes, France.
Rocher
J
J
Galanina
O
O
Bovin
N
N
Nifantev
N
N
Sherman
A
A
Cassagnau
E
E
Heymann
M F
MF
Bara
J
J
Fraser
R H
RH
Le Pendu
J
J
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D002240:Carbohydrate Sequence; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D000939:Epitopes / Q000276:immunology; D004903:Erythrocyte Aggregation / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology; D006026:Glycoside Hydrolases; D006031:Glycosylation; D006384:Hemagglutination / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000276:immunology / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D000939:Epitopes; D011134:Polysaccharides; D006026:Glycoside Hydrolases; C026093:keratan-sulfate endo-1,4-beta-galactosidase; D001616:beta-Galactosidase