Therapeutics: Thymic stromal lymphopoietin (TSLP); interleukin-33 (IL-33; NF-HEV); IL-25 (IL-17E)
Mouse studies suggest combined inhibition of IL-33, TSLP and IL-25 could help treat cytokine-driven inflammation and fibrosis. In a mouse model of Schistosomiasis mansoni infection, systemic knockout of TSLP and IL-33 plus an anti-IL-25 antibody decreased cytokine-induced inflammation and fibrosis in the liver compared with knockout or inhibition of any one of the targets. In a mouse model of allergy-induced chronic lung inflammation, systemic knockout of TSLP and IL-33 plus an anti-IL-25 antibody decreased inflammation in the lungs, recruitment of pro-inflammatory cytokines to the lungs and lung remodeling and fibrosis. Next steps could include testing the combination strategy in additional models of inflammation and fibrosis.
Amgen Inc. and AstraZeneca plc have tezepelumab (AMG 157; MEDI9929), a human antibody that blocks the interaction of TSLP and TSLP receptor (TSLPR; CRLF2), in Phase II testing to treat allergic asthma and atopic dermatitis. ...