Prospective Evaluation of Cetuximab-Mediated Antibody-Dependent Cell Cytotoxicity in Metastatic Colorectal Cancer Patients Predicts Treatment Efficacy.

摘要: Cetuximab is a monoclonal antibody to the EGFR that induces antibody-dependent cell cytotoxicity (ADCC) through Fcγ receptors on immune cells. Although SNPs in genes encoding are functionally relevant cetuximab-mediated ADCC colorectal cancer, direct correlation between vitro and clinical response cetuximab not defined. We therefore enrolled 96 consecutive metastatic cancer (mCRC) patients at diagnosis study assessed FcγR status ADCC. Patients carrying FcγRIIa H alleles 131H/Hand 131H/R had significantly higher compared with 131R/R (P= 0.013). FcγRIIIa genotypes V 158V/V 158V/F displayed 158F/F genotype 0.001). Progression-free survival of an 158V allele was longer 0.05), whereas no significant difference observed for overall survival. Twenty-eight 50 mCRC wild-type KRAS received cetuximab. The average ADCC-mediated killing 30% assay targets who experienced complete or partial response, 21% stable disease 9% progressive disease. To characterize basal natural killer (NK) activity, evaluated 39 patients. responded first-line treatment NK-cell cytotoxicity. Thus, although limited this cohort patients, correlated polymorphisms predicted responsiveness.