Monoclonal antibody G47 engineered to be reactive with colorectal tumor mucin.
We have previously shown that the normal adult colon produces a sialomucin containing the core trisaccharide 1,3 N-acetylgalactosamine. This structure was shown to be the epitope for a polyclonal antiserum that demonstrated colon "specific" activity. Antiserum binding is dependent upon the presence of O-acetylated sialic acids present at high concentrations in normal adult colon tissue. However, O-acetylation of sialic acids is decreased in colorectal cancer. Indeed, approximately 50% of colorectal carcinomas are nonreactive with this antiserum. In the current work, we used a de-O-acetylated, normal colon mucin as immunogen to generate monoclonal antibody (MAb) G47. Untreated normal colon mucins having a high O-acetylated sialic acid content were essentially nonreactive with G47. Removal of O-acetyl groups by saponification generated a reactive mucin derivative while subsequent treatment with neuraminidase abolished reactivity. By immunoperoxidase procedures MAb-G47 was reactive with approximately 85% of colorectal tumors while exhibiting relatively low reactivity with normal colon tissue. Mucins isolated from normal colon had on average less than 10% of the specific epitope as compared with mucins derived from colorectal tumors (p < 0.01). Initial immunohistochemical studies on tumors of noncolonic origin revealed few positive cases. The potential of MAb-G47 to assist in the diagnosis and/or prognosis of colorectal cancer is now being studied.
Gold
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DV
The Garden State Cancer Center, 520 Belleville Avenue, Belleville, NJ 07109, USA. dvgold@att.net
Cardillo
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TM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009077:Mucins / Q000276:immunology*; D052116:Sialomucins
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D009077:Mucins; D052116:Sialomucins