IL-17A pathway – a key target for immunotherapies

Published on May 12, 2016

IL 17-pathway-02 - final — Fig 1: Function of IL-17 in diverse processes

Interleukin-17 (IL-17) is a family of 6 closely related cytokines, designated IL-17A-F, that play a central role in mediating inflammation, autoimmunity, and host defense. IL-17 is mainly secreted by a specific subset of T helper cells known as T_H17 cells (for an overview see Fig 1). The IL-17 cytokines mediate their biological functions via surface receptors on target cells. IL-17A binds to IL-17 receptor A (IL-17RA), which stimulates the production of other pro-inflammatory cytokines including IL-6 and IL-8. IL-17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases such as rheumatoid arthritis. IL-17 signaling is also involved in mucosal immunity and host defense against extracellular bacterial and fungal infections (Staph, Candida, Pneumonia, etc.).

A target for immunotherapies

The IL-17A pathway is a key target for immunotherapies. The first therapeutic antibody that inhibits IL-17A signaling was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of psoriasis in 2015. Numerous pharmaceutical and biotech companies are developing biologics that target this pathway – for example, Amgen’s IL-17 receptor-specific antibody, brodalumab and Eli Lilly’s IL-17A-specific monoclonal, ixekizumab. In addition to psoriasis, IL-17 signaling is important in many other autoimmune and inflammatory diseases, including psoriatic and rheumatoid arthritis, Crohn’s disease, multiple sclerosis, and ankylosing spondylitis.

Versatile tools to screen for inhibitors of IL-17RA:IL-17A binding

Results inhibition — Fig 2: IL-17RA-IL-17A binding activity, measured using the IL-17RA[Biotin]-IL-17A Binding Assay Kit (14972060) and Anti-IL-17A Antibody (14991015). Luminescence was measured using a Bio-Tek fluorescent microplate reader.

To enable researchers to measure the inhibitory effect of compounds on IL-17RA:IL-17A binding BPS Bioscience has developed the IL-17RA:IL-17A Inhibitor Screening Assay Kit (available through tebu-bio in Europe).

The IL-17RA[Biotin]-IL-17A Binding Assay Kit comes in a 96-well format, with biotin-labeled IL-17RA, purified IL-17A, streptavidin-labeled HRP, and assay buffer for 100 binding reactions. The key to this kit is the high sensitivity of detection of biotin-labeled IL-17RA by streptavidin-HRP. Only a few simple steps on a microtiter plate are required for the assay. First, IL-17A is coated on a 96-well plate. Next, IL-17RA is incubated with IL-17A on the plate. Finally, the plate is treated with streptavidin-HRP followed by addition of an HRP substrate to produce chemiluminescence, which can then be measured using a chemiluminescence reader. The kit takes advantage of biotin-labeled IL-17RA to detect protein-protein interaction via Streptavidin-HRP and chemiluminescent detection in the same manner as other protein-protein interaction assays offered by BPS, such as PD-1:PD-L1 and PCSK9-LDLR. It provides researchers with a useful tool for screening small molecules or antibodies to block IL17A:IL17RA binding. The inhibition of IL-17RA:IL-17A binding by a neutralizing antibody is shown in Fig 2.

Besides the screening kit, BPS Biosciences also offers IL-17A and IL-17RA proteins and the the neutralizing (inhibiting) IL-17 antibody.

Interested in the IL-17RA:IL-17A Inhibitor Screening Assay Kit? Please get in touch with the form below.