Tk, a New Colon Tumor-associated Antigen Resulting from Altered O-Glycosylation
2000
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.
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