Cytokine Engineering Approaches for Regenerative Medicine

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Shiyi Li, Wenhao You, Mikaël M. Martino
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Abstract

Cytokines are central in orchestrating immune responses during tissue repair and regeneration, making them attractive candidates for regenerative medicine. However, their pleiotropic effects, short half-life, and poor biodistribution have limited their clinical translation. Advances in protein engineering have enabled the design of modified cytokines with enhanced stability, receptor selectivity, and tissue-targeting capabilities, offering new therapeutic opportunities for modulating immune activity and promoting tissue healing. Many of these engineering approaches have been pioneered in cancer immunotherapy, where cytokines are often designed to sustain inflammation and enhance cytotoxic immune responses. In contrast, regenerative medicine usually requires immune resolution, necessitating a distinct and sometimes opposite application of cytokine engineering strategies. This review explores the latest advancements in cytokine engineering for regenerative applications, focusing on strategies to enhance cytokine stability, modulate receptor affinity, improve targeting, and regulate endogenous cytokine signaling. Numerous approaches, highlighting how targeted immune modulation can enhance tissue healing while minimizing fibrosis and chronic inflammation, are discussed. These advances hold great promise for treating chronic wounds, fibrotic diseases, and tissue injuries with limited regenerative capacity, paving the way for precise, effective, and clinically translatable cytokine therapeutics. By adapting principles from cancer immunotherapy, cytokine-based therapies could transform regenerative medicine.

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再生医学中的细胞因子工程方法
细胞因子是组织修复和再生过程中协调免疫反应的核心,使其成为再生医学的有吸引力的候选者。然而,它们的多效性、半衰期短和生物分布差限制了它们的临床应用。蛋白质工程的进步使得修饰细胞因子的设计具有更高的稳定性、受体选择性和组织靶向能力,为调节免疫活性和促进组织愈合提供了新的治疗机会。许多这些工程方法已经在癌症免疫治疗中率先应用,其中细胞因子通常被设计用于维持炎症并增强细胞毒性免疫反应。相比之下,再生医学通常需要免疫解决方案,因此需要不同的,有时相反的细胞因子工程策略的应用。本文综述了细胞因子工程在再生应用中的最新进展,重点介绍了增强细胞因子稳定性、调节受体亲和力、提高靶向性和调节内源性细胞因子信号传导的策略。讨论了许多方法,强调如何靶向免疫调节可以增强组织愈合,同时最大限度地减少纤维化和慢性炎症。这些进展为治疗慢性伤口、纤维化疾病和再生能力有限的组织损伤带来了巨大的希望,为精确、有效和临床可翻译的细胞因子治疗铺平了道路。通过适应癌症免疫疗法的原理,基于细胞因子的疗法可以改变再生医学。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced Therapeutics
Advanced Therapeutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
7.10
自引率
2.20%
发文量
130
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