Freen-van Heeren Julian J
Independent Scientist, the Netherlands.
Cytokine X. 2020 Dec 21;3(1):100049. doi: 10.1016/j.cytox.2020.100049. eCollection 2021 Mar.
T cells are critical to fight pathogenic microbes and combat malignantly transformed cells in the fight against cancer. To exert their effector function, T cells produce effector molecules, such as the pro-inflammatory cytokines IFN-γ, TNF-α and IL-2. Tumors possess many inhibitory mechanisms that dampen T cell effector function, limiting the secretion of cytotoxic molecules. As a result, the control and elimination of tumors is impaired. Through recent advances in genomic editing, T cells can now be successfully modified via CRISPR/Cas9 technology. For instance, engaging (post-)transcriptional mechanisms to enhance T cell cytokine production, the retargeting of T cell antigen specificity or rendering T cells refractive to inhibitory receptor signaling can augment T cell effector function. Therefore, CRISPR/Cas9-mediated genome editing might provide novel strategies for cancer immunotherapy. Recently, the first-in-patient clinical trial was successfully performed with CRISPR/Cas9-modified human T cell therapy. In this review, a brief overview of currently available techniques is provided, and recent advances in T cell genomic engineering for the enhancement of T cell effector function for therapeutic purposes are discussed.
在对抗癌症的过程中，T细胞对于抵抗病原微生物和对抗恶性转化细胞至关重要。为发挥其效应功能，T细胞会产生效应分子，如促炎细胞因子IFN-γ、TNF-α和IL-2。肿瘤具有许多抑制机制，会削弱T细胞的效应功能，限制细胞毒性分子的分泌。因此，肿瘤的控制和消除受到损害。通过基因组编辑的最新进展，现在可以通过CRISPR/Cas9技术成功修饰T细胞。例如，利用（转录后）机制增强T细胞细胞因子的产生、重新靶向T细胞抗原特异性或使T细胞对抑制性受体信号传导产生抗性，都可以增强T细胞的效应功能。因此，CRISPR/Cas9介导的基因组编辑可能为癌症免疫治疗提供新策略。最近，首次在患者身上进行了CRISPR/Cas9修饰的人类T细胞疗法的临床试验。在这篇综述中，提供了当前可用技术的简要概述，并讨论了用于增强T细胞效应功能以达到治疗目的的T细胞基因组工程的最新进展。
