Engineering T Cells to Treat Cancer: The Convergence of Immuno-Oncology and Synthetic Biology

Engineering T Cells to Treat Cancer: The Convergence of Immuno-Oncology and Synthetic Biology
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DOI:
10.1146/annurev-cancerbio-030419-033657
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发表时间:
2020-01-01
期刊:
ANNUAL REVIEW OF CANCER BIOLOGY, VOL 4
影响因子:
--
通讯作者:
Lim, Wendell A.
Lim, Wendell A.
中科院分区:
其他
文献类型:
--
作者:
Choe, Joseph H.;Williams, Jasper Z.;Lim, Wendell A.

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经过基因工程改造以识别和杀伤肿瘤细胞的T细胞已成为对抗癌症的有力手段。然而,我们改造T细胞的能力仍然相对初级。除了用于治疗B细胞恶性肿瘤的嵌合抗原受体T细胞(CAR - T细胞)外,大多数T细胞疗法都有风险、有毒性,而且往往效果不佳,尤其是那些针对实体瘤的疗法。为了实现细胞疗法的前景,我们必须通过应用合成生物学的原理和工具,将细胞工程转变为一门系统的、可预测的科学。合成生物学采用一种分层的方法,组装模块化的分子部件组,这些部件可以组合成更大的回路和系统,以执行特定的目标任务。我们概述了克服实体瘤挑战所需的合成模块工具包、构建这些组件的进展,以及如何利用这些模块可靠地设计出更有效、更精准的T细胞疗法。
T cells engineered to recognize and kill ttunor cells have emerged as powerful agents for combating cancer. Nonetheless, our ability to engineer T cells remains relatively primitive. Aside from CAR T cells for treating B cell malignancies, most T cell therapies are risky, toxic, and often ineffective, especially those that target solid cancers. To fulfill the promise of cell -based therapies, we must transform cell engineering into a systematic and predictable science by applying the principles and tools of synthetic biology. Synthetic biology uses a hierarchical approach assembling sets of modular molecular parts that can lie combined into larger circuits and systems that perform defined target tasks. V\le outline the toolkit of synthetic modules that are needed to overcome the challenges of solid cancers, progress in building these components, and how these modules could lie used to reliably engineer more effective and precise T cell therapies.