Synthetic Biology in the Engineering of CAR-T and CAR-NK Cell Therapies: Facts and Hopes.
Synthetic Biology in the Engineering of CAR-T and CAR-NK Cell Therapies: Facts and Hopes.
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DOI：
10.1158/1078-0432.ccr-22-1491
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发表时间：
2023-04-14
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现代合成生物学工具的出现使得具有工程特异性的细胞治疗的发展成为可能，从而导致抗癌免疫治疗的新范式。T细胞一直处于这种发展的最前沿，在过去五年中，美国食品和药物管理局批准了六种嵌合抗原受体（CAR）修饰的T细胞产品用于治疗血液恶性肿瘤。自然杀伤（NK）细胞是具有强效细胞毒性活性的先天性淋巴细胞，并且由于其用于同种异体“现成”应用的潜力，它们已成为T细胞疗法的越来越有吸引力的替代方案。然而，T细胞和NK细胞都面临着许多挑战，包括抗原逃逸、免疫抑制性肿瘤微环境和潜在的严重毒性。已经开发了许多合成生物学策略来解决这些障碍，最常见的是在T细胞背景下。在这篇综述中，我们讨论了迄今为止开发的一系列策略，它们在NK细胞背景下的应用，以及临床翻译的机遇和挑战。
The advent of modern synthetic-biology tools has enabled the development of cellular treatments with engineered specificity, leading to a new paradigm in anti-cancer immunotherapy. T cells have been at the forefront of such development, with six chimeric antigen receptor (CAR)-modified T cell products approved by the United States Food and Drug Administration for the treatment of hematological malignancies in the last five 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.