A33 Background Information The A33 antigen is a transmembrane protein expressed almost exclusively in intestinal epithelium and in 95% of human colon cancers. Specifically, expression of the A33 protein occurs on the basolateral surfaces of intestinal epithelial cells of all lineages. The A33 antigen comprises an extracellular domain with two immunoglobulin-like domains, a single-span transmembrane domain, and a highly acidic cytoplasmic domain. Expression of A33 appears to be regulated by the intestine-specific homeobox transcription factor CDX1 and the gut-enriched Kruppel-like factor (GKLF). GKLF binds to the promoter region of the A33 gene in colon cancer cells, and mutations in the GKLF binding sequence leads to reduced expression of the A33 antigen. The therapeutic potential of administering the humanized monoclonal antibody A33 to colon cancer patients has proved encouraging.
