Abstract | PURPOSE: EXPERIMENTAL DESIGN: FcgammaRIIIa-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 FcgammaRIIIa. 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 FcgammaRIIIa polymorphisms on the clinical outcome of patients with SCCHN treated with alpha-EGFR mAbs.
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Authors | Rodney J Taylor, Siaw-Lin Chan, Aaron Wood, Caroline J Voskens, Jeffrey S Wolf, Wei Lin, Andrei Chapoval, Dan H Schulze, Guoliang Tian, Scott E Strome |
Journal | Cancer immunology, immunotherapy : CII
(Cancer Immunol Immunother)
Vol. 58
Issue 7
Pg. 997-1006
(Jul 2009)
ISSN: 1432-0851 [Electronic] Germany |
PMID | 18979096
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- FCGR3A protein, human
- Receptors, IgG
- Cetuximab
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Topics |
- Alleles
- Antibodies, Monoclonal
(immunology, therapeutic use)
- Antibodies, Monoclonal, Humanized
- Antibody-Dependent Cell Cytotoxicity
(genetics, immunology)
- Antineoplastic Agents
(immunology, therapeutic use)
- Carcinoma, Squamous Cell
(drug therapy, immunology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cetuximab
- Head and Neck Neoplasms
(drug therapy, immunology)
- Humans
- Killer Cells, Natural
(immunology, metabolism)
- Polymorphism, Genetic
- Receptors, IgG
(genetics, immunology)
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