A Mutant Chaperone Converts a Wild-Type Protein into a Tumor-Specific Antigen.

ANTIGENS; MONOCLONAL antibodies; TUMORS; THERAPEUTICS; CANCER vaccines; PROTEINS; GLYCOSYLTRANSFERASES; MONOSACCHARIDES; ONCOGENIC viruses

Monoclonal antibodies have become important therapeutic agents against certain cancers. Many tumor-specific antigens are mutant proteins that are predominantly intracellular and thus not readily accessible to monoclonal antibodies. We found that a wild-type transmembrane protein could be transformed into a tumor-specific antigen. A somatic mutation in the chaperone gene Cosmc abolished function of a glycosyltransferase, disrupting O-glycan Core 1 synthesis and creating a tumor-specific glycopeptidic neo-epitope consisting of a monosaccharide and a specific wild-type protein sequence. This epitope induced a high-affinity, highly specific, syngeneic monoclonal antibody with antitumor activity. Such tumor-specific glycopeptidic neo-epitopes represent potential targets for monoclonal antibody therapy. [ABSTRACT FROM AUTHOR]

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