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Human IgG₃ Monoclonal Antibody Directed to an Unbranched Repeating Type 2 Chain (Galß14GlcNAcß13Galß14GlcNAcß13Galß1R) Which Is Highly Expressed in Colonic and Hepatocellular Carcinoma¹

The Biomembrane Institute and University of Washington, 201 Elliott Avenue West, Seattle, Washington

Previously established human monoclonal antibodies (MAbs) directed to carbohydrate antigens are essentially all IgM class, and show relatively low affinity and low reactivity at 37°C. We report here the establishment of a human IgG₃ MAb displaying high affinity antigen-binding activity at 37°C and efficiently activating cellular cytotoxicity directed to human tumor cell lines expressing the polylactosamine antigen. The IgG₃ MAb (MH21–134) reacted with the repeated unbranched polylactosamine structure Galß14GlcNAcß13Galß14GlcNAcß13Galß1R, i.e., nLc₆, nLc₈, etc., but did not react with sialyl 23 or 26 substituted derivatives at the terminal Gal. This specificity differs from that of several anti-i antibodies, or human anti-i-like MAbs which react with sialyl 23 substituted structures. Directly biotinylated MH21–134 antibody was used in immunohistochemical staining of 154 formalin-fixed, paraffin-embedded tissue sections to study distribution of the antigen. High incidence of positive staining was found in colon cancer (11/17; 65%) and hepatocellular carcinoma (8/12; 67%), followed by large cell and squamous cell carcinoma of lung cancer (10/13; 59%, and 14/26; 54%, respectively). TLC immunostaining of glycolipid extracts from a variety of tumor tissues showed the presence of nLc₆ and/or nLc₈ in over 50% of cases. The antigens nLc₆ and nLc₈ were found to be absent from normal colonic epithelia, kidney, and pancreas. Only a weak band corresponding to nLc₈ and one corresponding to nLc₆ were found in liver and spleen, although all these normal tissues, including gastrointestinal epithelia, lung, liver, spleen, erythrocytes, and lymphocytes, were essentially negative on immunohistology. However, the antigen was found to be highly expressed in myelocytes and weakly in bronchial glands of lung and pancreatic duct epithelia. Nevertheless, expression of unsubstituted, unbranched polylactosamine antigen could be an important basis for induction of humoral immune response against certain types of human cancer, despite its limited expression in normal cells.

¹ This study was supported by funds from The Biomembrane Institute and in part by Outstanding Investigator Grant (OIG) CA42505 from the National Cancer Institute.

² Senior Fellow, Department of Pathobiology, University of Washington, and The Biomembrane Institute.

Received 1/30/89. Revised 6/29/89. Accepted 7/13/89.

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