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Pancreatic cancer

IL-17; IL-17 receptor (IL17R; IL17RA)

Human sample and mouse studies suggest inhibiting IL-17 signaling could help treat pancreatic cancer. Chronic pancreatitis accelerates pancreatic cancer, and chronic inflammation can induce pancreatic intraepithelial neoplasias (PanINs). In human tissue arrays, IL17R expression was greater in pancreatic lesions, including PanINs, than normal acinar tissue. In a mouse model of inducible pancreatitis that progresses to PanIN, Il-17 was expressed in Cd4+ T cells, and depletion of Cd4+ T cells delayed progression. In the mice, a cocktail of anti-IL17R and anti-IL-17 mAbs decreased PanINs on the pancreas surface and the number of advanced PanINs compared with saline. Next steps include neutralizing IL-17 signaling in more advanced metastatic disease models and identifying patients that would benefit from IL-17 inhibition.
Amgen Inc., AstraZeneca plc and Kyowa Hakko Kirin Co. Ltd. have brodalumab, a humanized mAb against IL17R, in Phase III or earlier testing to treat autoimmune and inflammatory indications.
At least seven companies have antibodies against IL-17 in Phase II or earlier testing to treat various indications.

SciBX 7(24); doi:10.1038/scibx.2014.706
Published online June 19, 2014

Unpatented; licensing status not applicable

McAllister, F. et al. Cancer Cell;
published online May 12, 2014;
Contact: Steven D. Leach, The Johns Hopkins University, Baltimore, Md.