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Article: FcγRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and neck

TitleFcγRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and neck
Authors
KeywordsAdcc
Cetuximab
Nk
Polymorphisms
Scchn
Issue Date2009
PublisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00262/index.htm
Citation
Cancer Immunology, Immunotherapy, 2009, v. 58 n. 7, p. 997-1006 How to Cite?
AbstractPurpose: The interaction of Fc fragments of antibodies with the Fcγ receptors is an essential checkpoint in antibody-dependent cellular cytotoxicity (ADCC). Specific polymorphisms at position 158 enhance FcγRIIIa affinity for IgG1 and are associated with improved clinical outcome in lymphoma patients treated with IgG1 anti-CD20 antibody. The role of ADCC in the therapeutic effects of the α-epidermal growth factor receptor (EGFR) mAb, cetuximab, in patients with squamous cell carcinoma of the head and neck (SCCHN) is poorly defined. We employed three SCCHN cell lines to test two hypotheses: (1) SCCHN is susceptible to cetuximab-mediated ADCC, (2) efficacy of ADCC is associated with polymorphisms at position 158 of FcγRIIIa. Experimental design: FcγRIIIa-158 polymorphisms were determined for healthy donors, and their purified NK cells were used as effector cells against three SCCHN cell lines in ADCC assays. Cytotoxicity levels were compared for each polymorphism class. Proliferation and cell cycle assays were done to examine the direct effects of cetuximab. Results: Our results indicate that SCCHN is susceptible to cetuximab-mediated ADCC in vitro. NK cytotoxic efficiency correlates with donor 158-polymorphisms in FcγRIIIa. Overall cytotoxicity was greatest for individuals having a single V allele when compared to homozygous F/F individuals; the cumulative percent cytotoxicity for each polymorphism among the cell lines was 58.2% V/V, 50.6% V/F, and 26.1% F/F (P < 0.001). Additionally, the presence of a V allele correlated with superior natural cytotoxicity against NK sensitive targets. Conclusion: These data have both prognostic and therapeutic relevance and support the design of a prospective trial to determine the influence of FcγRIIIa polymorphisms on the clinical outcome of patients with SCCHN treated with α-EGFR mAbs. © 2008 Springer-Verlag.
Persistent Identifierhttp://hdl.handle.net/10722/172459
ISSN
2015 Impact Factor: 4.846
2015 SCImago Journal Rankings: 2.066
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTaylor, RJen_US
dc.contributor.authorChan, SLen_US
dc.contributor.authorWood, Aen_US
dc.contributor.authorVoskens, CJen_US
dc.contributor.authorWolf, JSen_US
dc.contributor.authorLin, Wen_US
dc.contributor.authorChapoval, Aen_US
dc.contributor.authorSchulze, DHen_US
dc.contributor.authorTian, Gen_US
dc.contributor.authorStrome, SEen_US
dc.date.accessioned2012-10-30T06:22:38Z-
dc.date.available2012-10-30T06:22:38Z-
dc.date.issued2009en_US
dc.identifier.citationCancer Immunology, Immunotherapy, 2009, v. 58 n. 7, p. 997-1006en_US
dc.identifier.issn0340-7004en_US
dc.identifier.urihttp://hdl.handle.net/10722/172459-
dc.description.abstractPurpose: The interaction of Fc fragments of antibodies with the Fcγ receptors is an essential checkpoint in antibody-dependent cellular cytotoxicity (ADCC). Specific polymorphisms at position 158 enhance FcγRIIIa affinity for IgG1 and are associated with improved clinical outcome in lymphoma patients treated with IgG1 anti-CD20 antibody. The role of ADCC in the therapeutic effects of the α-epidermal growth factor receptor (EGFR) mAb, cetuximab, in patients with squamous cell carcinoma of the head and neck (SCCHN) is poorly defined. We employed three SCCHN cell lines to test two hypotheses: (1) SCCHN is susceptible to cetuximab-mediated ADCC, (2) efficacy of ADCC is associated with polymorphisms at position 158 of FcγRIIIa. Experimental design: FcγRIIIa-158 polymorphisms were determined for healthy donors, and their purified NK cells were used as effector cells against three SCCHN cell lines in ADCC assays. Cytotoxicity levels were compared for each polymorphism class. Proliferation and cell cycle assays were done to examine the direct effects of cetuximab. Results: Our results indicate that SCCHN is susceptible to cetuximab-mediated ADCC in vitro. NK cytotoxic efficiency correlates with donor 158-polymorphisms in FcγRIIIa. Overall cytotoxicity was greatest for individuals having a single V allele when compared to homozygous F/F individuals; the cumulative percent cytotoxicity for each polymorphism among the cell lines was 58.2% V/V, 50.6% V/F, and 26.1% F/F (P < 0.001). Additionally, the presence of a V allele correlated with superior natural cytotoxicity against NK sensitive targets. Conclusion: These data have both prognostic and therapeutic relevance and support the design of a prospective trial to determine the influence of FcγRIIIa polymorphisms on the clinical outcome of patients with SCCHN treated with α-EGFR mAbs. © 2008 Springer-Verlag.en_US
dc.languageengen_US
dc.publisherSpringer Verlag. The Journal's web site is located at http://link.springer.de/link/service/journals/00262/index.htmen_US
dc.relation.ispartofCancer Immunology, Immunotherapyen_US
dc.subjectAdccen_US
dc.subjectCetuximaben_US
dc.subjectNken_US
dc.subjectPolymorphismsen_US
dc.subjectScchnen_US
dc.titleFcγRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and necken_US
dc.typeArticleen_US
dc.identifier.emailTian, G: gltian@hku.hken_US
dc.identifier.authorityTian, G=rp00789en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1007/s00262-008-0613-3en_US
dc.identifier.pmid18979096-
dc.identifier.scopuseid_2-s2.0-65549139376en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-65549139376&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume58en_US
dc.identifier.issue7en_US
dc.identifier.spage997en_US
dc.identifier.epage1006en_US
dc.identifier.isiWOS:000265575100001-
dc.publisher.placeGermanyen_US
dc.identifier.scopusauthoridTaylor, RJ=7405757953en_US
dc.identifier.scopusauthoridChan, SL=25627548200en_US
dc.identifier.scopusauthoridWood, A=7401883108en_US
dc.identifier.scopusauthoridVoskens, CJ=24765663400en_US
dc.identifier.scopusauthoridWolf, JS=7403565201en_US
dc.identifier.scopusauthoridLin, W=36068291300en_US
dc.identifier.scopusauthoridChapoval, A=6701644618en_US
dc.identifier.scopusauthoridSchulze, DH=7102867976en_US
dc.identifier.scopusauthoridTian, G=25621549400en_US
dc.identifier.scopusauthoridStrome, SE=7004882323en_US
dc.identifier.citeulike3646875-

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