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Non-small cell lung cancer (NSCLC)


Mouse studies suggest blocking IL-17 could help treat or prevent inflammatory chronic obstructive pulmonary disease (COPD)-associated NSCLC. In a mouse model of early NSCLC, inoculation of COPD-generating lysates from Haemophilus influenza increased tumor growth, which was associated with higher T helper type 17 (Th17) cell numbers, compared with no inoculation. In lysate-treated mice with NSCLC, Il-17 knockout decreased tumor growth compared with Il-17f knockout. Antibody-mediated depletion of Il-17-recruited myeloid cells also decreased tumor growth compared with no alteration. Next steps include investigating other reagents that could block Th17 cells such as IL-23-specific antibodies or RAR-related orphan receptor C thymus-specific isoform (RORg2; RORgT) inhibitors.
Brodalumab, a humanized mAb against IL-17 receptor (IL17R; IL17RA) from Amgen Inc. and partners AstraZeneca plc and Kyowa Hakko Kirin Co. Ltd., is in Phase III testing to treat psoriasis and Phase II trials to treat asthma, psoriatic arthritis and inflammatory diseases.
At least eight other companies have compounds that block IL-17 signaling in Phase II or earlier development to treat various autoimmune and inflammatory diseases.

SciBX 7(17); doi:10.1038/scibx.2014.491
Published online May 1, 2014

Unpatented; licensing status not applicable

Chang, S.H. et al. Proc. Natl. Acad. Sci. USA; published online
March 31, 2014;
Contact: Seyed Javad Moghaddam, The University of Texas MD Anderson Cancer Center, Houston, Texas
Contact: Seon Hee Chang, same affiliation as above