文章：

CRISPR-Cas基因敲除以优化用于癌症免疫治疗的工程化T细胞

CRISPR-Cas gene knockouts to optimize engineered T cells for cancer immunotherapy 

原文发布日期：2024-04-12 

英文摘要：

While CAR-T and tgTCR-T therapies have exhibited noteworthy and promising outcomes in hematologic and solid tumors respectively, a set of distinct challenges remains. Consequently, the quest for novel strategies has become imperative to safeguard and more effectively release the full functions of engineered T cells. These factors are intricately linked to the success of adoptive cell therapy. Recently, CRISPR-based technologies have emerged as a major breakthrough for maintaining T cell functions. These technologies have allowed the discovery of T cells’ negative regulators such as specific cell-surface receptors, cell-signaling proteins, and transcription factors that are involved in the development or maintenance of T cell dysfunction. By employing a CRISPR-genic invalidation approach to target these negative regulators, it has become possible to prevent the emergence of hypofunctional T cells. This review revisits the establishment of the dysfunctional profile of T cells before delving into a comprehensive summary of recent CRISPR-gene invalidations, with each invalidation contributing to the enhancement of engineered T cells’ antitumor capacities. The narrative unfolds as we explore how these advancements were discovered and identified, marking a significant advancement in the pursuit of superior adoptive cell therapy. 

摘要翻译：

尽管CAR-T和tgTCR-T疗法分别在血液肿瘤和实体瘤治疗中展现出显著且具有前景的疗效，但仍面临一系列独特挑战。因此，寻找新策略以保障并更有效释放工程化T细胞的全部功能已成为当务之急。这些因素与过继细胞疗法的成功密切相关。近期，基于CRISPR的技术已成为维持T细胞功能的重大突破，该技术成功揭示了T细胞负向调控因子（包括特定细胞表面受体、细胞信号蛋白及转录因子）在T细胞功能障碍形成或维持中的作用。通过采用CRISPR基因敲除手段靶向这些负向调控因子，现已成为预防T细胞功能低下的有效途径。本文在重新审视T细胞功能障碍特征建立的基础上，系统综述了近期CRISPR基因敲除研究进展——每一次基因敲除都致力于增强工程化T细胞的抗肿瘤能力。通过探索这些发现的取得与验证过程，我们将展现这一追求卓越过继细胞疗法道路上的重大进步。

原文链接：

CRISPR-Cas gene knockouts to optimize engineered T cells for cancer immunotherapy