Glycoprotein A33 (GPA33) (GPA33)

Glycoprotein A33 (GPA33) is a 43 kDa transmembrane protein belonging to the immunoglobulin superfamily, primarily expressed in the intestinal epithelium (UniProt Q99795). It is a highly specific marker for colorectal cancer, found in over 95% of primary and metastatic cases, while its normal expression is restricted to the gastric and intestinal mucosa (PMID: 15150570). The protein is known for its high stability on the cell surface, as it does not undergo significant internalization or shedding, making it an ideal target for radioimmunotherapy and imaging. In recent years, GPA33-positive exosomes have emerged as significant biomarkers in liquid biopsies, allowing for the non-invasive monitoring of colorectal cancer progression (PMID: 30135554). Therapeutic development has focused on monoclonal antibodies, radio-labeled ligands, and bispecific T-cell engagers like MGD007 (PMID: 30030305). While targeting GPA33 is effective for tumor localization, the primary safety concern involves potential damage to the normal intestinal lining, which also expresses the antigen, leading to gastrointestinal toxicities such as colitis.

Other names

A33 antigenCell surface A33 antigenGPA33

Antibody-dependent cellular cytotoxicity (ADCC), Radioimmunotherapy, T-cell redirection