Details

Autor(en) / Beteiligte

• Sasaki-Iwaoka, Haruna
• Ohori, Makoto
• Imasato, Akira
• Taguchi, Katsunari
• Minoura, Kyoko
• Saito, Tetsu
• Kushima, Kiyoshi
• Imamura, Emiko
• Kubo, Satoshi
• Furukawa, Shigetada
• Morokata, Tatsuaki

Titel

Generation and characterization of a potent fully human monoclonal antibody against the interleukin-23 receptor

Ist Teil von

• European journal of pharmacology, 2018-06, Vol.828, p.89-96

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Quelle

ScienceDirect

Beschreibungen/Notizen

• Interleukin (IL)-12 and IL-23 share a common subunit (p40) and function in T-helper (Th) 1 and Th17 immunity, respectively. Anti-IL-12/23p40 and specific anti-IL-23 antibodies are currently in clinical use for psoriasis and undergoing trials for autoimmune diseases. Since expression levels of the IL-23 receptor are likely to be much lower than those of IL-23, an anti-IL-23 receptor antibody might offer greater promise in inhibiting the IL-23-IL-17 pathways involved in inflammatory disorders. To our knowledge, no anti-IL-23 receptor antibody has been trialed in clinical studies to date. This study describes the generation and characterization of AS2762900-00, a fully human monoclonal antibody against the IL-23 receptor. AS2762900-00 bound both human and cynomolgus monkey IL-23 receptors. AS2762900-00 showed potent inhibitory effects on IL-23-induced Kit-225 cell proliferation compared to the existing anti-IL-12/23p40 antibody, ustekinumab. In a single dose administration pharmacodynamics study in cynomolgus monkeys, 1 mg/kg of AS2762900-00 significantly inhibited (> 85%) IL-23-induced STAT3 phosphorylation in blood for up to 84 days. Therefore, AS2762900-00 represents a potent novel IL-23-IL-17 pathway inhibitor with the potential to be developed into a new therapy for the treatment of autoimmune diseases.