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合成生物学在 CAR-T 和 CAR-NK 细胞疗法工程化中的应用:事实与希望

英文原题:Synthetic Biology in the Engineering of CAR-T and CAR-NK Cell Therapies: Facts and Hopes.

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Synthetic Biology in the Engineering of CAR-T and CAR-NK Cell Therapies: Facts and Hopes.

PubMed 2023/04/14(内容时间) Clin Cancer Res Q1 · IF 10.9(JCR 2025)

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中文摘要

现代合成生物学工具的出现使得开发具有工程化特异性的细胞疗法成为可能,从而引领了抗癌免疫治疗的新范式。T细胞一直处于此类开发的最前沿,过去5年中已有6款经FDA批准的嵌合抗原受体修饰T细胞产品用于治疗血液系统恶性肿瘤。自然杀伤(NK)细胞是具有强效细胞毒活性的固有淋巴细胞,由于其具有用于同种异体“现货型”应用的潜力,已成为T细胞疗法日益具有吸引力的替代选择。然而,T细胞和NK细胞均面临诸多挑战,包括抗原逃逸、免疫抑制性肿瘤微环境以及严重毒性的潜在风险。为应对这些障碍,已开发出多种合成生物学策略,最常见的是在T细胞背景下。在本综述中,我们讨论了迄今为止已开发的各类策略、它们在NK细胞背景下的应用,以及临床转化的机遇与挑战。

展开英文摘要原文

The advent of modern synthetic-biology tools has enabled the development of cellular treatments with engineered specificity, leading to a new paradigm in anticancer immunotherapy. T cells have been at the forefront of such development, with six chimeric antigen receptor-modified T-cell products approved by the FDA for the treatment of hematologic malignancies in the last 5 years.

Natural killer (NK) cells are innate lymphocytes with potent cytotoxic activities, and they have become an increasingly attractive alternative to T-cell therapies due to their potential for allogeneic, "off-the-shelf" applications.

However, both T cells and NK cells face numerous challenges, including antigen escape, the immunosuppressive tumor microenvironment, and potential for severe toxicity. Many synthetic-biology strategies have been developed to address these obstacles, most commonly in the T-cell context. In this review, we discuss the array of strategies developed to date, their application in the NK-cell context, as well as opportunities and challenges for clinical translation.

论文信息

作者
Clubb JD、Gao TA、Chen YY
单位
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California.United States
文献类型
综述 · 美国 NIH 资助研究 · 非美国政府资助研究
期刊
Clinical cancer research : an official journal of the American Association for Cancer Research2023 Apr 14
原文标识
PubMed 36454122 · DOI 10.1158/1078-0432.CCR-22-1491