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增强肿瘤免疫应答的合成生物学方法

英文原题:Synthetic biology approaches to enhance cancer immune responses.

查看英文原题

Synthetic biology approaches to enhance cancer immune responses.

PubMed 2025/11/27(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

合成生物学正被广泛应用于肿瘤治疗,从减弱微生物毒性到构建合成基因回路以及开发 CAR-T 细胞,这些都在重塑癌症免疫治疗的格局。在这篇综述中,我们总结了基于微生物的治疗方法的最新进展,这些方法利用细菌对缺氧肿瘤区域的天然趋向性,以高空间精度递送免疫调节有效载荷。CAR-T 细胞工程方面的平行进展促成了装甲型和逻辑门控构建体的开发,旨在克服抗原异质性、免疫抑制性肿瘤微环境和 T 细胞耗竭等挑战。合成生物学通过能够执行布尔逻辑运算的可编程基因回路进一步整合这些平台,确保仅在肿瘤特异性生物标志物存在时才激活治疗。尽管这种融合在重编程抗肿瘤免疫方面提供了前所未有的精度、安全性和效力,但这些复杂系统的临床转化面临重大障碍。尽管临床转化存在挑战——包括安全性问题、免疫清除和制造复杂性——该领域正朝着多功能“智能”疗法、协同微生物-细胞组合以及个性化治疗策略迈进。

总之,这些创新正在定义新一代精准工程化免疫疗法,有望改变难治性恶性肿瘤的治疗。

展开英文摘要原文

Synthetic biology is being widely applied in tumor therapy, ranging from attenuating microbial toxicity to constructing synthetic gene circuits and developing CAR-T cells, all of which are reshaping the landscape of cancer immunotherapy. In this review, we summarize recent advances in microbial-based therapeutics that leverage bacteria's natural tropism for hypoxic tumor regions to deliver immunomodulatory payloads with high spatial precision. Parallel progress in CAR-T cell engineering has led to the development of armored and logic-gated constructs designed to overcome challenges such as antigen heterogeneity, the immunosuppressive tumor microenvironment, and T cell exhaustion.

Synthetic biology further integrates these platforms via programmable genetic circuits capable of performing Boolean logic operations, ensuring therapeutic activation only in the presence of tumor-specific biomarkers. While this convergence offers the unprecedented precision, safety, and potency in reprogramming anti-tumor immunity, the clinical translation of these complex systems faces significant hurdles.

Despite challenges in clinical translation-including safety concerns, immune clearance, and manufacturing complexity-the field is advancing toward multifunctional "smart" therapies, synergistic microbial-cell combinations, and personalized treatment strategies.

Together, these innovations are defining a new generation of precision-engineered immunotherapies with the potential to transform the treatment of refractory malignancies.

论文信息

作者
Liu S、Zhong Z、Tu Q、Jin M
单位
Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.China
文献类型
综述
期刊
Frontiers in immunology2025
原文标识
PubMed 41394856 · DOI 10.3389/fimmu.2025.1698158