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Cynomolgus monkey model of interleukin‐31‐induced scratching depicts blockade of human interleukin‐31 receptor A by a humanized monoclonal antibody
Author(s) -
Oyama Sohei,
Kitamura Hidetomo,
Kuramochi Taichi,
Higuchi Yoshinobu,
Matsushita Hiroaki,
Suzuki Tsukasa,
Goto Masaaki,
Adachi Hideki,
Kasutani Keiko,
Sakamoto Akihisa,
Iwayanagi Yuki,
Kaneko Akihisa,
Nanami Masahiko,
Fujii Etsuko,
Esaki Keiko,
Takashima Yoshiaki,
Shimaoka Shin,
Hattori Kunihiro,
Kawabe Yoshiki
Publication year - 2018
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13236
Subject(s) - scratching , atopic dermatitis , monoclonal antibody , medicine , blockade , immunology , interleukin , subcutaneous injection , antibody , receptor antagonist , pathogenesis , receptor , pharmacology , cytokine , antagonist , endocrinology , physics , acoustics
Scratching is an important factor exacerbating skin lesions through the so‐called itch‐scratch cycle in atopic dermatitis ( AD ). In mice, interleukin ( IL )‐31 and its receptor IL ‐31 receptor A ( IL ‐31 RA ) are known to play a critical role in pruritus and the pathogenesis of AD ; however, study of their precise roles in primates is hindered by the low sequence homologies between primates and mice and the lack of direct evidence of itch sensation by IL ‐31 in primates. We showed that administration of cynomolgus IL ‐31 induces transient scratching behaviour in cynomolgus monkeys and by that were able to establish a monkey model of scratching. We then showed that a single subcutaneous injection of 1 mg/kg nemolizumab, a humanized anti‐human IL ‐31 RA monoclonal antibody that also neutralizes cynomolgus IL ‐31 signalling and shows a good pharmacokinetic profile in cynomolgus monkeys, suppressed the IL ‐31‐induced scratching for about 2 months. These results suggest that the IL ‐31 axis and IL ‐31 RA axis play as critical a role in the induction of scratching in primates as in mice and that the blockade of IL ‐31 signalling by an anti‐human IL ‐31 RA antibody is a promising therapeutic approach for treatment of AD . Nemolizumab is currently under investigation in clinical trials.