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延长半衰期抗体:特应性皮炎管理新方法的叙述性综述

Extended Half-life Antibodies: A Narrative Review of a New Approach in the Management of Atopic Dermatitis.

作者信息

Yilmaz Orhan, Torres Tiago

机构信息

College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada.

Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.

出版信息

Dermatol Ther (Heidelb). 2024 Sep;14(9):2393-2406. doi: 10.1007/s13555-024-01253-6. Epub 2024 Aug 15.

Abstract

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions, significantly impacting physical health and quality of life. The pathogenesis of AD involves genetic predisposition, immune dysregulation, and environmental factors, with a defective skin barrier playing a crucial role. Treatment options for AD include both topical and systemic therapies, with advanced treatments like Janus kinase inhibitors and biologics offering significant improvements but facing limitations in safety and dosing frequency. Extended half-life antibodies represent a promising advancement for the management of immune-mediated inflammatory diseases, including AD. These antibodies, engineered for prolonged circulation and reduced dosing frequency, target key cytokines and immune pathways known to be involved in the pathogenesis of AD, offering potential for less frequent administration while maintaining efficacy. Currently, two such agents are in phase 2 trials. APG777, targeting interleukin-13 (IL-13), and IMG-007, targeting OX40 receptor, have shown promising preclinical and early clinical results. They demonstrated prolonged half-lives and the potential for less frequent dosage regimen, along with significant improvements in AD symptoms. These therapies could enhance patient adherence and reduce healthcare burdens by decreasing injection frequencies and clinic visits. As research continues, extended half-life antibodies could significantly improve AD management and patient quality of life. Further studies will determine the long-term safety and efficacy of extended half-life antibodies, with ongoing innovations in antibody engineering likely to broaden their applications and benefits.

摘要

特应性皮炎(AD)是一种慢性炎症性皮肤病,其特征为剧烈瘙痒和湿疹样皮损,对身体健康和生活质量有显著影响。AD的发病机制涉及遗传易感性、免疫失调和环境因素,皮肤屏障功能缺陷起着关键作用。AD的治疗选择包括局部和全身治疗,像 Janus 激酶抑制剂和生物制剂等先进治疗方法虽有显著改善,但在安全性和给药频率方面存在局限性。延长半衰期抗体是治疗免疫介导的炎症性疾病(包括AD)的一项有前景的进展。这些经过设计以实现延长循环时间和降低给药频率的抗体,靶向已知参与AD发病机制的关键细胞因子和免疫途径,在维持疗效的同时具有减少给药频率的潜力。目前,有两种此类药物正处于2期试验阶段。靶向白细胞介素-13(IL-13)的APG777和靶向OX40受体的IMG-007已显示出有前景的临床前和早期临床结果。它们展现出延长的半衰期以及采用较低给药频率方案的潜力,同时AD症状有显著改善。这些疗法可通过减少注射频率和门诊就诊次数来提高患者依从性并减轻医疗负担。随着研究的持续进行,延长半衰期抗体可能会显著改善AD的管理和患者生活质量。进一步的研究将确定延长半衰期抗体的长期安全性和疗效,抗体工程领域正在进行的创新可能会拓宽其应用范围和益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9bd/11393227/cbffb9e56e19/13555_2024_1253_Fig1_HTML.jpg

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