FcγR polymorphisms and clinical outcome in colorectal cancer patients receiving passive or active antibody treatment

Abstract

Fc gamma receptors (Fc gamma Rs) on effector cells are of importance for mediating antibody-dependent cellular cytotoxicity (ADCC) Fc gamma RIIIa158valine (V)/phenylalanine (F) and Fc gamma RIIa131 histidine (H)/arginine(R) polymorphisms have been shown to relate to prognosis in antibody-treated patients The aim of the present study was to analyze the polymorphisms of both Fc gamma RIIIa and Fc gamma RIIa in colorectal carcinoma (CRC) patients receiving either passively administered monoclonal antibodies (MAbs) or antibodies induced by carcinoembryonic antigen (CEA) vaccination One hundred and thirty CRC patients were included Thirty-eight patients received adjuvant treatment with an anti-EpCAM monoclonal antibody (edrecolomab) (n=17) or rCEA vaccination therapeutic cancer vaccine (TCV) (n=21) inducing anti-CEA IgG antibodies Ninety-two patients had metastatic disease and received anti-EpCAM MAb based therapies Fc gamma R genotypes were analysed using genomic DNA and PCR ADCC was tested in a standard 18 h Cr-51 release assay In all adjuvant-treated patients, Fc gamma RIIIa158V carriers (V/V and V/F) had a significantly better overall survival compared to F/F homozygous patients (p<0 05), Fc gamma RIIa R carriers vs H/H (p=0 05) as well as V and R carriers combined compared to the others (p<0 05) Similar findings were obtained when antibody and TCV-treated patients were analysed separately No impact on the prognosis of Fc gamma R polymorphisms was noted in advanced disease Fc gamma RIIIa V carriers had a significantly higher ADCC activity compared to F/F patients (p=0 001) Our model study might support the notion that Fc gamma RIIIa V carriers as well as Fc gamma RIIa R carriers receiving adjuvant, passively or actively (TCV)-induced antibody treatment might have a better prognosis than the others Prospective extended clinical trials are warranted to study the predictive/prognostic Impact of Fc gamma R polymorphisms in antibody-treated patients and might be a valuable biomarker to optimize antibody-based treatment strategies