Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, 30322, USA.
Department of Pediatrics, Emory School of Medicine, Atlanta, GA, 30322, USA.
Adv Healthc Mater. 2021 Aug;10(15):e2002214. doi: 10.1002/adhm.202002214. Epub 2021 Mar 9.
Cytokine signaling is critical to a range of biological processes including cell development, tissue repair, aging, and immunity. In addition to acting as key signal mediators of the immune system, cytokines can also serve as potent immunotherapies with more than 20 recombinant products currently Food and Drug Administration (FDA)-approved to treat conditions including hepatitis, multiple sclerosis, arthritis, and various cancers. Yet despite their biological importance and clinical utility, cytokine immunotherapies suffer from intrinsic challenges that limit their therapeutic potential including poor circulation, systemic toxicity, and low tissue- or cell-specificity. In the past decade in particular, methods have been devised to engineer cytokines in order to overcome such challenges and here, the myriad strategies are reviewed that may be employed in order to improve the therapeutic potential of cytokine and chemokine immunotherapies with applications in cancer and autoimmune disease therapy, as well as tissue engineering and regenerative medicine. For clarity, these strategies are collected and presented as they vary across size scales, ranging from single amino acid substitutions, to larger protein-polymer conjugates, nano/micrometer-scale particles, and macroscale implants. Together, this work aims to provide readers with a timely view of the field of cytokine engineering with an emphasis on early-stage therapeutic approaches.
细胞因子信号转导对于一系列生物学过程至关重要，包括细胞发育、组织修复、衰老和免疫。除了作为免疫系统的关键信号介质外，细胞因子还可以作为有效的免疫疗法，目前已有 20 多种重组产品获得美国食品和药物管理局（FDA）批准，用于治疗包括肝炎、多发性硬化症、关节炎和各种癌症在内的多种疾病。然而，尽管细胞因子免疫疗法具有重要的生物学意义和临床应用价值，但它们仍存在内在的挑战，限制了其治疗潜力，包括循环不良、全身毒性和低组织或细胞特异性。特别是在过去十年中，人们设计了多种方法来工程化细胞因子，以克服这些挑战。在这里，我们综述了可以用于提高细胞因子和趋化因子免疫疗法治疗癌症和自身免疫性疾病以及组织工程和再生医学的治疗潜力的各种策略。为了清晰起见，这些策略是按照大小尺度进行收集和呈现的，从单个氨基酸取代到更大的蛋白-聚合物缀合物、纳米/微米级颗粒和宏观植入物。总之，这项工作旨在为读者提供细胞因子工程领域的最新观点，重点介绍早期治疗方法。
