Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab

Cancer Immunology Research
Rodney J TaylorEzra E W Cohen

Abstract

We conducted in vitro studies and a clinical trial for patients with squamous cell carcinoma of the head and neck (SCCHN) to study the relationship between FcγRIIIa polymorphisms and antibody-dependent cellular cytotoxicity (ADCC). In vitro, FcγRIIIa genotype was correlated with ADCC and innate cytotoxicity using natural killer (NK) cells harvested from healthy donors. In the phase II study, patients with recurrent or metastatic SCCHN were treated with cetuximab (500 mg/m(2) i.v. every 2 weeks) and lenalidomide (25 mg daily). FcγRIIIa genotype and ex vivo ADCC were correlated with clinical response, progression-free survival (PFS), and overall survival (OS). In vitro, healthy donors with a FcγRIIIa 158-V allele demonstrated more effective ADCC against two colon cancer cell lines HT29 and SW480, mean cytotoxicity: FF 16.1%, VF/VV 24.3% (P = 0.015) and FF 11.7%, VF/VV 21.0% (P = 0.008), respectively. We observed a linear relationship between ADCC response and innate cytotoxicity. In the phase II trial, 40 patients received cetuximab and lenalidomide with median PFS of 7.2 weeks and OS of 16.4 weeks. Thirty-six patients had FcγRIIIa genotype: VV (2), VF (20), and FF (14), and 25 patients had sufficient NK-cell yield to perform ex ...Continue Reading

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Citations

Dec 19, 2015·Cancer Cell·Lorenzo GalluzziGuido Kroemer
Nov 17, 2015·Hematology/oncology Clinics of North America·David W Schoppy, John B Sunwoo
May 31, 2019·Frontiers in Immunology·Daniel E GeraghtyRasmi Thomas
Mar 11, 2020·Frontiers in Immunology·Aviad Ben-ShmuelMira Barda-Saad
May 2, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Laura K van DijkJohan Bussink
Nov 1, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Amy K ErbePaul M Sondel
Feb 20, 2021·Critical Reviews in Oncology/hematology·Mélanie GauthierVéronique Decot
May 3, 2021·Journal of Translational Medicine·Shiqi LongXing Zhao

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