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

The Pharmacogenomics Journal volume 14, pages 14–19 (2014)Cite this article

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Abstract

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 FcγR 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 FcγRIIIa 158 V/V genotype had a significantly higher cetuximab-mediated ADCC. No correlation was found between FcγR polymorphisms and response rate or time to progression after cetuximab-based therapy. Despite the in vitro analysis showing that the FcγRIIIa 158 V/V genotype is associated with higher ADCC, clinical data do not support a predictive role of FcγRIIIa polymorphisms in mCRC treated with cetuximab.

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Acknowledgements

This work was supported in part by the Cariparma Foundation (Fondazione Cassa di Risparmio di Parma, Parma, Italy).

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Author notes

  1. F V Negri and A Musolino: These authors contributed equally to this work.

Authors and Affiliations

  1. Medical Oncology Unit and Medical Genetics Unit, University Hospital of Parma, Parma, Italy

    F V Negri, A Musolino, N Naldi, B Bortesi, R Camisa, T M Neri & A Ardizzoni

  2. Department of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, University Hospital of Parma, Parma, Italy

    G Missale & D Laccabue

  3. Department of Laboratory Medicine, Clinical Microbiology Laboratory, Santa Maria Nuova Hospital, Reggio Emilia, Italy

    A Zerbini

  4. Department of Radiology University Hospital of Parma, Parma, Italy

    N Chernyschova

  5. Department of Oncology, IRCCS, Santa Maria Nuova Hospital, Reggio Emilia, Italy

    G Bisagni

  6. Division of Medical Oncology, Department of Oncology, Transplants and New Technologies in Medicine, University of Pisa, Pisa, Italy

    F Loupakis

  7. Department of Biomolecular Sciences, University of Urbino, Urbino, Italy

    A Ruzzo

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  1. F V Negri
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Correspondence to F V Negri.

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Negri, F., Musolino, A., Naldi, N. et al. Role of immunoglobulin G fragment C receptor polymorphism-mediated antibody-dependant cellular cytotoxicity in colorectal cancer treated with cetuximab therapy. Pharmacogenomics J 14, 14–19 (2014). https://doi.org/10.1038/tpj.2012.54

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  • DOI: https://doi.org/10.1038/tpj.2012.54

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