TY - JOUR T1 - <strong>ASP7266, a novel antibody against human thymic stromal lymphopoietin receptor </strong><strong>for the treatment of allergic diseases</strong> JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.121.000686 SP - JPET-AR-2021-000686 AU - Mako Numazaki AU - Masaki Abe AU - Kaori Hanaoka AU - Emiko Imamura AU - Masashi Maeda AU - Akihiko Kimura AU - Jun Miyanohara AU - Tetsu Saito AU - Kazunori Arai AU - Hiroshi Suzuki AU - Yuji Saita Y1 - 2021/01/01 UR - http://jpet.aspetjournals.org/content/early/2021/11/02/jpet.121.000686.abstract N2 - Thymic stromal lymphopoietin (TSLP), positioned at the top of the inflammatory cascade, is a key regulator that enhances allergic inflammatory responses by activating T helper type 2 (Th2) cells, Group 2 innate lymphoid cells (ILC2), and myeloid dendritic cells (mDCs) via the TSLP receptor (TSLPR). We evaluated the inhibitory effects of ASP7266, a novel recombinant fully human IgG1 monoclonal antibody against TSLPR, on TSLP signaling and inflammation. The inhibitory effects of ASP7266 and the control antibody tezepelumab on TSLP and TSLPR interactions were investigated using a proliferation assay with TSLP stimulation and a chemokine production assay. The pharmacological effects of ASP7266 were investigated by examining differentiation of naive CD4+ T cells, ILC2 cytokine production, and ascaris extract-induced skin allergic reaction in cynomolgus monkeys. ASP7266 potently inhibited TSLP-induced cell proliferation and C-C motif chemokine ligand 17 (CCL17) production. Furthermore, ASP7266 inhibited TSLP-stimulated mDC-mediated naive CD4+ T cell differentiation, and IL-5 production by lineage-negative peripheral blood mononuclear cells (PBMCs), which can be considered ILC2, in vitro. In sensitized monkeys, ASP7266 completely suppressed ascaris extract-induced allergic skin reactions. Based on these results, ASP7266, a novel human therapeutic antibody against TSLPR, is a potential therapy for patients with allergic diseases. Significance Statement TSLP, positioned at the top of the inflammatory cascade, plays a key role in various allergic diseases, including asthma, chronic rhinosinusitis with nasal polyposis, and atopic dermatitis. Here we show that the anti-TSLPR antibody, ASP7266, exhibited excellent pharmacological activity in preclinical studies. Therefore, ASP7266 has the potential to be a promising treatment option for patients with allergic disorders. ER -