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肿瘤免疫治疗中合成生物学回路的工程原理

英文原题:Engineering Principles for Synthetic Biology Circuits in Cancer Immunotherapy.

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Engineering Principles for Synthetic Biology Circuits in Cancer Immunotherapy.

PubMed 2022/01/01(内容时间) Cancer Immunol Res Q1 · IF 7.9(JCR 2025)

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中文摘要

近年来,生物分子工程的进展催生了具有精密编程功能的新型癌症免疫疗法,包括嵌合抗原受体(CAR)T细胞,其可结合肿瘤相关抗原(TAA)以引导协调的免疫应答。大量的工程化努力不仅致力于编程CAR特异性,还致力于编程激活分子应答的下游通路。总体而言,这些努力可以被概念化为一个免疫治疗回路:TAA作为输入信号结合CAR;细胞内信号级联将结合相互作用处理为转录和翻译事件;这些事件编程效应输出功能。更简单地说,这一序列可以抽象为输入、处理和输出。在本综述中,我们讨论了癌症免疫治疗中合成生物学解决方案日益复杂的图景,并在免疫治疗回路的框架内总结了近期工作。通过这样做,可以建立一个基本模块化回路的工具箱,作为基础,在此基础上可以构建精密的解决方案以应对更复杂的问题。参见第5页的相关文章。

展开英文摘要原文

Recent advances in biomolecular engineering have led to novel cancer immunotherapies with sophisticated programmed functions, including chimeric antigen receptor (CAR) T cells that bind tumor-associated antigens (TAA) to direct coordinated immune responses. Extensive engineering efforts have been made to program not only CAR specificity, but also downstream pathways that activate molecular responses. Collectively, these efforts can be conceptualized as an immunotherapy circuit: TAAs bind the CAR as input signals; intracellular signaling cascades process the binding interactions into transcriptional and translational events; and those events program effector output functions.

More simply, this sequence may be abstracted as input, processing, and output. In this review, we discuss the increasingly complex scene of synthetic-biology solutions in cancer immunotherapy and summarize recent work within the framework of immunotherapy circuits. In doing so, a toolbox of basic modular circuits may be established as a foundation upon which sophisticated solutions can be constructed to meet more complex problems. See related article on p. 5.

论文信息

作者
Shih RM、Chen YY
第一作者单位
Department of Molecular Biology, University of California, Los Angeles (UCLA), Los Angeles, California.United States
通讯作者单位
Department of Molecular Biology, University of California, Los Angeles (UCLA), Los Angeles, California. yvchen@ucla.edu.United States
文献类型
美国 NIH 资助研究 · 非美国政府资助研究 · 综述
期刊
Cancer immunology research2022 Jan
原文标识
PubMed 34983828 · DOI 10.1158/2326-6066.CIR-21-0769