Overcoming the limitations of cytokines to improve cancer therapy
Overcoming the limitations of cytokines to improve cancer therapy
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DOI：
10.1016/bs.ircmb.2022.05.002
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发表时间：
2022-01-01
期刊：
影响因子：
--
通讯作者：
Berraondo, Pedro
中科院分区：
文献类型：
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作者：
Augusta Di Trani, Claudia;Cirella, Assunta;Berraondo, Pedro
细胞因子是一种多效性可溶性蛋白，被免疫细胞用于协调对抗病原体和恶性肿瘤的反应。在癌症免疫治疗中，基于细胞因子的药物可以增强促炎细胞因子或阻断免疫抑制细胞因子。然而，细胞因子作用机制的复杂性要求使用生物技术策略来最小化全身毒性，同时增强抗肿瘤反应。采用序列突变、融合蛋白和基因治疗策略来延长循环中的半衰期，针对肿瘤微环境靶向所需的生物活性，优化细胞因子的治疗窗口。在这篇综述中，我们概述了目前在临床前和临床研究中所追求的不同策略，以充分利用细胞因子进行癌症免疫治疗。
Cytokines are pleiotropic soluble proteins used by immune cells to orchestrate a coordinated response against pathogens and malignancies. In cancer immunotherapy, cytokine-based drugs can be developed potentiating pro-inflammatory cytokines or blocking immunosuppressive cytokines. However, the complexity of the mechanisms of action of cytokines requires the use of biotechnological strategies to minimize systemic toxicity, while potentiating the antitumor response. Sequence mutagenesis, fusion proteins and gene therapy strategies are employed to enhance the half-life in circulation, target the desired bioactivity to the tumor microenvironment, and to optimize the therapeutic window of cytokines. In this review, we provide an overview of the different strategies currently being pursued in pre-clinical and clinical studies to make the most of cytokines for cancer immunotherapy.