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

  • Authors:
    • Biyun Wang
    • Parviz Kokhaei
    • Håkan Mellstedt
    • Maria Liljefors
  • View Affiliations

  • Published online on: December 1, 2010     https://doi.org/10.3892/ijo_00000814
  • Pages: 1599-1606
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Fcγ receptors (FcγRs) on effector cells are of importance for mediating antibody-dependent cellular cytotoxicity (ADCC). FcγRIIIa158valine (V)/phenylalanine (F) and FcγRIIa131histidine (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 FcγRIIIa and FcγRIIa 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. FcγR genotypes were analysed using genomic DNA and PCR. ADCC was tested in a standard 18 h Cr51 release assay. In all adjuvant-treated patients, FcγRIIIa158V carriers (V/V and V/F) had a significantly better overall survival compared to F/F homozygous patients (p<0.05), FcγRIIa 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 FcγR polymorphisms was noted in advanced disease. FcγRIIIa V carriers had a significantly higher ADCC activity compared to F/F patients (p=0.001). Our model study might support the notion that FcγRIIIa V carriers as well as FcγRIIa 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 FcγR polymorphisms in antibody-treated patients and might be a valuable biomarker to optimize antibody-based treatment strategies.

Related Articles

Journal Cover

December 2010
Volume 37 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Wang B, Kokhaei P, Mellstedt H and Liljefors M: FcγR polymorphisms and clinical outcome in colorectal cancer patients receiving passive or active antibody treatment. Int J Oncol 37: 1599-1606, 2010.
APA
Wang, B., Kokhaei, P., Mellstedt, H., & Liljefors, M. (2010). FcγR polymorphisms and clinical outcome in colorectal cancer patients receiving passive or active antibody treatment. International Journal of Oncology, 37, 1599-1606. https://doi.org/10.3892/ijo_00000814
MLA
Wang, B., Kokhaei, P., Mellstedt, H., Liljefors, M."FcγR polymorphisms and clinical outcome in colorectal cancer patients receiving passive or active antibody treatment". International Journal of Oncology 37.6 (2010): 1599-1606.
Chicago
Wang, B., Kokhaei, P., Mellstedt, H., Liljefors, M."FcγR polymorphisms and clinical outcome in colorectal cancer patients receiving passive or active antibody treatment". International Journal of Oncology 37, no. 6 (2010): 1599-1606. https://doi.org/10.3892/ijo_00000814