Monoclonal Antibody G47 Engineered to be Reactive with Colorectal Tumor Mucin

Abstract

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.

Expression of a colorectal antigen defined by a new monoclonal antibody, CO-TL1

“…1 As a result of these mutations and subsequent transformations 'unique' tumour antigens have emerged, to which monoclonal antibodies were generated 2,3 like the Adnab-9 antibodies, 4 DAS-1 antibody, 5 G47 antibodies. 6 On the other hand, monoclonal antibodies to antigens that are not unique but common for both the normal cell type and the derived tumour cells might serve equally well as markers. Antibodies to intermediate filaments (vimentin, neurofilament, keratin) have been amply used to trace tissue-specific origin of tumours.…”