OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target.

Autor: Croft M; Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, CA, 92037, USA. mick@lji.org., Esfandiari E; Kyowa Kirin International, London, UK., Chong C; Kyowa Kirin International, London, UK., Hsu H; Amgen Inc., Thousand Oaks, CA, USA., Kabashima K; Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Kricorian G; Amgen Inc., Thousand Oaks, CA, USA., Warren RB; Dermatology Centre, Northern Care Alliance NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK., Wollenberg A; Department of Dermatology and Allergy, Ludwig-Maximilian-University, Munich, Germany.; Department of Dermatology and Allergy, University Hospital Augsburg, Augsburg, Germany., Guttman-Yassky E; Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1047, New York, NY, 10029-6574, USA. emma.guttman@mountsinai.org.; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY, USA. emma.guttman@mountsinai.org.
Jazyk: angličtina
Zdroj: American journal of clinical dermatology [Am J Clin Dermatol] 2024 May; Vol. 25 (3), pp. 447-461. Date of Electronic Publication: 2024 Jan 18.
DOI: 10.1007/s40257-023-00838-9
Abstrakt: Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD.
(© 2024. The Author(s).)
Databáze: MEDLINE
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