2. Academic Validation
  3. An S100A8/A9 Neutralizing Antibody Potently Ameliorates Contact Hypersensitivity and Atopic Dermatitis Symptoms

An S100A8/A9 Neutralizing Antibody Potently Ameliorates Contact Hypersensitivity and Atopic Dermatitis Symptoms

  • J Invest Dermatol. 2025 Jan 21:S0022-202X(25)00029-6. doi: 10.1016/j.jid.2025.01.007.
Yuma Gohara 1,  Rie Kinoshita 1,  Nahoko Tomonobu 1,  Fan Jiang 1,  Yukiko Matsunaga 2,  Yuki Hashimoto 2,  Tomoko Honjo 3,  Ken-Ichi Yamamoto 1,  Hitoshi Murata 1,  Toshiki Ochi 4,  Ni Luh Gede Yoni Komalasari 5,  Akira Yamauchi 6,  Futoshi Kuribayashi 6,  Yoshihiko Sakaguchi 7,  Junichiro Futami 3,  Yusuke Inoue 8,  Eisaku Kondo 9,  Shinichi Toyooka 10,  Shin Morizane 11,  Akira Ishiko 2,  Shigeru Morita 12,  Kazumi Sagayama 13,  Kenichiro Nakao 14,  Masakiyo Sakaguchi 15
Affiliations

Affiliations

  • 1 Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • 2 Department of Dermatology, Toho University Graduate School of Medicine, Tokyo, Japan.
  • 3 Department of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, Japan.
  • 4 Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • 5 Faculty of Medicine, Udayana University, Denpasar, Indonesia.
  • 6 Department of Biochemistry, Kawasaki Medical School, Kurashiki, Japan.
  • 7 Department of Microbiology, Tokushima Bunri University, Sagamihara, Japan.
  • 8 Division of Molecular Science, Faculty of Science and Technology, Gunma University, Kiryu, Japan.
  • 9 Division of Tumor Pathology, Near-Infrared Photo-Immunotherapy Research Institute, Kansai Medical University, Osaka, Japan.
  • 10 Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • 11 Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • 12 Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan.
  • 13 Organization for Research and Innovation Strategy, Okayama University, Okayama, Japan.
  • 14 Nobelpharma, Tokyo, Japan.
  • 15 Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: masa-s@md.okayama-u.ac.jp.
PMID: 39848567 DOI: 10.1016/j.jid.2025.01.007
Abstract

Contact hypersensitivity and atopic dermatitis are pervasive inflammatory skin diseases with similar symptoms, and their global prevalence is steadily increasing. Many compounds and biotics have been developed to target molecules critical to the etiology or pathogenesis of contact hypersensitivity and atopic dermatitis. However, these molecules are sometimes ineffective or lose their potency during the therapeutic course. Therefore, innovative medicines are still needed for the treatment of intractable cases. We focused on S100A8/A9, a heterodimer complex of S100A8 and S100A9 that is abundant in the extracellular milieu of inflammatory skin lesions. Although S100A8/A9 is primarily recognized as a diagnostic marker protein, we have previously shown that it also plays a crucial role in contact hypersensitivity and atopic dermatitis progression. This insight inspired us to develop its inhibitory antibody, leading to the ground-breaking Ab45. In this study, we demonstrated that Ab45 effectively prevented disease symptoms in various models and that its disease-ameliorating activity likely involved the downregulation of several disease-relevant molecules, including Il-23a, Il-36g, S100a8, and S100a9. We also created a humanized version of Ab45, HuAb45, which exhibited similar effectiveness. These Antibodies show great promise for the treatment of contact hypersensitivity and atopic dermatitis and possibly for Other inflammatory skin diseases.

Keywords

Atopic dermatitis; Contact hypersensitivity; Humanized antibody; Inflammation; S100 protein.

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