Anti-IL-17A Antibody (Ixekizumab)

Ixekizumab, also known as LY2439821,is a humanized IgG4 monoclonal antibody that selectively binds and neutralizes interleukin IL-17A. It directly blocks IL-17A binding to IL-17RA (IL-17receptor) but does not bind other IL-17 family members. Ixekizumab is used for the research of moderate-to-severe plaque psoriasis. IL-17A, originally known as CTLA-8 (cytotoxic T lymphocyte-associated antigen 8), is a cytokine crucial in infection and inflammatory processes. It is the most studied of the IL-17 family, which consists of six structurally related proteins: IL-17A to IL-17F. It is produced in macrophages, dendritic cells, and gammadelta-T cells. It signals via the IL-17R (IL-17 receptor) family of proteins, which includes the subunits IL-17RA-E, and are single-pass transmembrane receptors. Signaling occurs via a heterodimeric receptor typically composed of IL-17RA and a second chain. Upon binding of IL-17 to the receptor, Act1 (Act 1 adaptor protein) is activated and TRAF6 (TNF receptor associated factor 6) is recruited. Ubiquitinated TRAF6 leads to the expression of inflammatory related genes, via the NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway. IL-17 dysregulation can result in psoriasis and other auto-immune disorders. The use of monoclonal antibodies able to block IL-17R have proved beneficial in the treatment of plaque psoriasis and rheumatic disorders, and bimekizumab, brodalumab, secukinumab and ixekizumab are already approved by the FDA.