体内 CAR 基因治疗的前景与潜在陷阱
Promises and potential pitfalls of in vivo CAR gene therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Overcoming the limitations of cytokines to improve cancer therapy.
Overcoming the limitations of cytokines to improve cancer therapy.
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细胞因子是免疫细胞用来协调针对病原体和恶性肿瘤的协同反应的多效性可溶性蛋白。在癌症免疫治疗中,可以开发基于细胞因子的药物,增强促炎细胞因子或阻断免疫抑制性细胞因子。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大限度地降低全身毒性,同时增强抗肿瘤反应。序列诱变、融合蛋白和基因治疗策略被用于提高循环中的半衰期,将所需的生物活性靶向肿瘤微环境,并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正在探索的不同策略,以最大限度地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.
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