The use of
monoclonal antibodies as adjuvants to
cancer chemotherapy has drawn considerable interest in recent years, due to the success of several novel agents against a broad range of targets. One such target is
EpCAM (aka GA733-2, KSA, 17-1A
antigen), a human
cell surface glycoprotein expressed on some normal and most neoplastic epithelial cells. It is now widely recognized as having an important role in
tumor biology, especially in
colorectal cancer, and since its original discovery in the early 1980s, the known mechanism by which it functions has steadily evolved. Initial studies of
monoclonal antibodies directed against
EpCAM demonstrated the presence of anti-idiotype networks involving both B and T cells, antibody-dependent cell cytotoxicity, and
complement mediated cell death as mechanisms of
tumor growth inhibition. Recently, a novel receptor for
EpCAM has been described that is a member of the inhibitory group of
immunoglobulin-like receptors and is present on lymphocytes, monocytes, dendritic cells, and NK cells. Neoplastic cells that interact with this receptor, named LAIR-1, may enact an immunologic escape, and thus confer a selective advantage for their growth and spread. This novel mechanism of action may add to our current understanding of how
monoclonal antibodies targeted against
EpCAM inhibit
tumor growth. Passive vaccination with this antibody may induce a tertiary anti-idiotypic network which correlates with clinical outcome, but the mechanism behind this outcome in select patients with
minimal residual disease may additionally involve a novel blockade of
tumor specific immunosuppression. This review will focus on the initial discoveries of
EpCAM's cellular adhesion properties, its role in normal and neoplastic cell function, its distribution and presumed mechanism of action, and clinical studies of
EpCAM as a therapeutic target. Clinical trials of
edrecolomab, one such
monoclonal antibody, in patients with
colon cancer will be reviewed and updated. While phase III trials of
edrecolomab have not demonstrated improved efficacy as adjuvant
therapy for stage III
colon cancer, newer agents with improved affinity, less chimerism, and improved delivery may still demonstrate benefit.