Role of immunoglobulin G fragment C receptor polymorphism-mediated antibody-dependant cellular cytotoxicity in colorectal cancer treated with cetuximab therapy

Antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was proposed as a mechanism of cetuximab efficacy. Peripheral blood mononuclear cells (PBMCs) from 23 healthy donors and 13 patients with metastatic colorectal cancer (mCRC) treated with cetuximab were tested for Fc gamma R polymorphisms and cetuximab-mediated ADCC. ADCC was measured by chromium-51 release on a epidermal growth factor receptor (EGFR)-positive human colon cancer cell line. Overall, 86 mCRC patients were genotyped for study purposes. PBMCs harbouring the Fc gamma RIIIa 158 V/V genotype had a significantly higher cetuximab-mediated ADCC. No correlation was found between Fc gamma R polymorphisms and response rate or time to progression after cetuximab-based therapy. Despite the in vitro analysis showing that the Fc gamma RIIIa 158 V/V genotype is associated with higher ADCC, clinical data do not support a predictive role of FcgRIIIa polymorphisms in mCRC treated with cetuximab.