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Epidermal growth factor receptor (EGFR); tumor necrosis factor receptor superfamily member 9 (TNFRSF9; 4-1BB; CD137)

Studies in mice and human samples suggest sequential treatment with anti-EGFR and anti-CD137 antibodies could help treat EGFR+ tumors. In EGFR+ mouse xenograft and syngeneic tumor models, the anti-EGFR mAb Erbitux cetuximab increased the number of Cd137+ NK cells in blood, spleen and tumors, and subsequent treatment with BMS-663513, an anti-CD137 antibody, increased tumor regression and prolonged survival compared with either antibody alone. In samples from patients with head and neck cancer, Erbitux increased the number of CD137+ NK cells by 4%-15% compared with pretreatment numbers. Next steps include designing a clinical trial of anti-EGFR plus anti-CD137 antibodies.
Eli Lilly and Co., Bristol-Myers Squibb Co. and Merck KGaA market Erbitux to treat colorectal and head and neck cancer.
Amgen Inc. markets the anti-EGFR mAb Vectibix panitumumab to treat colorectal and other types of cancer.
BMS-663513 is in Phase I trials to treat solid tumors.
Pfizer Inc.'s anti-CD137 antibody, PF-05082566, is in Phase I trials to treat cancers including non-Hodgkin's lymphoma (NHL).

SciBX 7(25); doi:10.1038/scibx.2014.732
Published online June 26, 2014

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Kohrt, H.E. et al. J. Clin. Invest.; published online May 16, 2014;
Contact: Holbrook E. Kohrt, Stanford University Medical Center, Stanford, Calif.