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

Rodney J. Taylor, Vassiliki Saloura, Ajay Jain, Olga Goloubeva, Stuart Wong, Shari Kronsberg, Madhavi Nagilla, Lorna Silpino, Jonas De Souza, Tanguy Lim Seiwert, Everett Vokes, Victoria Villaflor, Ezra E.W. Cohen

Research output: Contribution to journalArticle

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/m2 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 vivo ADCC. FcγRIIIa genotype was not associated with any clinical outcomes. Patients mounting ex vivo ADCC response had a higher likelihood of stable disease (P= 0.01) and showed a trend toward increased PFS: 14 weeks versus 6.8 weeks, respectively (P = 0.13). Enhanced ex vivo ADCC and innate immunity responses were more predictive of clinical response than FcγRIIIa and may offer a functional assay to select patients suitable for cetuximab therapy.

Original languageEnglish (US)
Pages (from-to)567-574
Number of pages8
JournalCancer Immunology Research
Volume3
Issue number5
DOIs
StatePublished - May 1 2015
Externally publishedYes

Fingerprint

Antibodies
Genotype
Disease-Free Survival
Natural Killer Cells
Tissue Donors
Survival
Cetuximab
Innate Immunity
Cellular Immunity
Colonic Neoplasms
Alleles
Clinical Trials
Cell Line
In Vitro Techniques
Carcinoma, squamous cell of head and neck
lenalidomide
Therapeutics

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

Cite this

Taylor, R. J., Saloura, V., Jain, A., Goloubeva, O., Wong, S., Kronsberg, S., ... Cohen, E. E. W. (2015). Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab. Cancer Immunology Research, 3(5), 567-574. https://doi.org/10.1158/2326-6066.CIR-14-0188

Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab. / Taylor, Rodney J.; Saloura, Vassiliki; Jain, Ajay; Goloubeva, Olga; Wong, Stuart; Kronsberg, Shari; Nagilla, Madhavi; Silpino, Lorna; De Souza, Jonas; Lim Seiwert, Tanguy; Vokes, Everett; Villaflor, Victoria; Cohen, Ezra E.W.

In: Cancer Immunology Research, Vol. 3, No. 5, 01.05.2015, p. 567-574.

Research output: Contribution to journalArticle

Taylor, RJ, Saloura, V, Jain, A, Goloubeva, O, Wong, S, Kronsberg, S, Nagilla, M, Silpino, L, De Souza, J, Lim Seiwert, T, Vokes, E, Villaflor, V & Cohen, EEW 2015, 'Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab', Cancer Immunology Research, vol. 3, no. 5, pp. 567-574. https://doi.org/10.1158/2326-6066.CIR-14-0188
Taylor, Rodney J. ; Saloura, Vassiliki ; Jain, Ajay ; Goloubeva, Olga ; Wong, Stuart ; Kronsberg, Shari ; Nagilla, Madhavi ; Silpino, Lorna ; De Souza, Jonas ; Lim Seiwert, Tanguy ; Vokes, Everett ; Villaflor, Victoria ; Cohen, Ezra E.W. / Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab. In: Cancer Immunology Research. 2015 ; Vol. 3, No. 5. pp. 567-574.
@article{f111fee2862e48dc850912bb131c0686,
title = "Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab",
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/m2 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 vivo ADCC. FcγRIIIa genotype was not associated with any clinical outcomes. Patients mounting ex vivo ADCC response had a higher likelihood of stable disease (P= 0.01) and showed a trend toward increased PFS: 14 weeks versus 6.8 weeks, respectively (P = 0.13). Enhanced ex vivo ADCC and innate immunity responses were more predictive of clinical response than FcγRIIIa and may offer a functional assay to select patients suitable for cetuximab therapy.",
author = "Taylor, {Rodney J.} and Vassiliki Saloura and Ajay Jain and Olga Goloubeva and Stuart Wong and Shari Kronsberg and Madhavi Nagilla and Lorna Silpino and {De Souza}, Jonas and {Lim Seiwert}, Tanguy and Everett Vokes and Victoria Villaflor and Cohen, {Ezra E.W.}",
year = "2015",
month = "5",
day = "1",
doi = "10.1158/2326-6066.CIR-14-0188",
language = "English (US)",
volume = "3",
pages = "567--574",
journal = "Cancer immunology research",
issn = "2326-6066",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Ex vivo antibody-dependent cellular cytotoxicity inducibility predicts efficacy of cetuximab

AU - Taylor, Rodney J.

AU - Saloura, Vassiliki

AU - Jain, Ajay

AU - Goloubeva, Olga

AU - Wong, Stuart

AU - Kronsberg, Shari

AU - Nagilla, Madhavi

AU - Silpino, Lorna

AU - De Souza, Jonas

AU - Lim Seiwert, Tanguy

AU - Vokes, Everett

AU - Villaflor, Victoria

AU - Cohen, Ezra E.W.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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/m2 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 vivo ADCC. FcγRIIIa genotype was not associated with any clinical outcomes. Patients mounting ex vivo ADCC response had a higher likelihood of stable disease (P= 0.01) and showed a trend toward increased PFS: 14 weeks versus 6.8 weeks, respectively (P = 0.13). Enhanced ex vivo ADCC and innate immunity responses were more predictive of clinical response than FcγRIIIa and may offer a functional assay to select patients suitable for cetuximab therapy.

AB - 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/m2 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 vivo ADCC. FcγRIIIa genotype was not associated with any clinical outcomes. Patients mounting ex vivo ADCC response had a higher likelihood of stable disease (P= 0.01) and showed a trend toward increased PFS: 14 weeks versus 6.8 weeks, respectively (P = 0.13). Enhanced ex vivo ADCC and innate immunity responses were more predictive of clinical response than FcγRIIIa and may offer a functional assay to select patients suitable for cetuximab therapy.

UR - http://www.scopus.com/inward/record.url?scp=84962277989&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962277989&partnerID=8YFLogxK

U2 - 10.1158/2326-6066.CIR-14-0188

DO - 10.1158/2326-6066.CIR-14-0188

M3 - Article

C2 - 25769300

AN - SCOPUS:84962277989

VL - 3

SP - 567

EP - 574

JO - Cancer immunology research

JF - Cancer immunology research

SN - 2326-6066

IS - 5

ER -