肿瘤坏死因子α
阿达木单抗
类风湿性关节炎
医学
银屑病
英夫利昔单抗
体内
免疫学
依那西普
妥珠单抗
白细胞介素17
药理学
细胞因子
癌症研究
生物
生物技术
作者
Michela Silacci,Wibke Lembke,Richard D. Woods,Isabella Attinger-Toller,Nadja Baenziger-Tobler,Sarah Batey,Roger Santimaria,Ulrike von der Bey,Susann Koenig-Friedrich,Wenjuan Zha,Bernd Schlereth,Mathias Locher,Julian Bertschinger,Dragan Grabulovski
出处
期刊:mAbs
[Informa]
日期:2015-09-22
卷期号:8 (1): 141-149
被引量:79
标识
DOI:10.1080/19420862.2015.1093266
摘要
Biologic treatment options such as tumor necrosis factor (TNF) inhibitors have revolutionized the treatment of inflammatory diseases, including rheumatoid arthritis. Recent data suggest, however, that full and long-lasting responses to TNF inhibitors are limited because of the activation of the pro-inflammatory TH17/interleukin (IL)-17 pathway in patients. Therefore, dual TNF/IL-17A inhibition is an attractive avenue to achieve superior efficacy levels in such diseases. Based on the marketed anti-TNF antibody adalimumab, we generated the bispecific TNF/IL-17A-binding FynomAb COVA322. FynomAbs are fusion proteins of an antibody and a Fyn SH3-derived binding protein. COVA322 was characterized in detail and showed a remarkable ability to inhibit TNF and IL-17A in vitro and in vivo. Through its unique mode-of-action of inhibiting simultaneously TNF and the IL-17A homodimer, COVA322 represents a promising drug candidate for the treatment of inflammatory diseases. COVA322 is currently being tested in a Phase 1b/2a study in psoriasis ( ClinicalTrials.gov Identifier: NCT02243787).
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