利用 CRISPR-Cas 基因敲除技术优化用于癌症免疫疗法的工程 T 细胞

IF 4.8 3区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Valentine De Castro, Jeanne Galaine, Romain Loyon, Yann Godet
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引用次数: 0

摘要

虽然 CAR-T 疗法和 tgTCR-T 疗法分别在血液肿瘤和实体瘤方面取得了令人瞩目和充满希望的成果,但仍然存在一系列独特的挑战。因此,寻求新策略以保护和更有效地释放工程 T 细胞的全部功能已成为当务之急。这些因素与采纳细胞疗法的成功密切相关。最近,基于 CRISPR 的技术成为维持 T 细胞功能的重大突破。这些技术发现了 T 细胞的负调控因子,如特定的细胞表面受体、细胞信号蛋白和转录因子,它们参与了 T 细胞功能障碍的形成或维持。通过采用 CRISPR-genic 无效方法来靶向这些负调控因子,就有可能防止出现功能低下的 T 细胞。本综述在全面总结最近的CRISPR基因无效研究之前,先重温了T细胞功能障碍特征的建立,每一种无效研究都有助于增强工程T细胞的抗肿瘤能力。当我们探索这些进展是如何被发现和确定时,叙述就展开了,这标志着在追求卓越的收养细胞疗法方面取得了重大进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

CRISPR-Cas gene knockouts to optimize engineered T cells for cancer immunotherapy
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.
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来源期刊
Cancer gene therapy
Cancer gene therapy 医学-生物工程与应用微生物
CiteScore
10.20
自引率
0.00%
发文量
150
审稿时长
4-8 weeks
期刊介绍: Cancer Gene Therapy is the essential gene and cellular therapy resource for cancer researchers and clinicians, keeping readers up to date with the latest developments in gene and cellular therapies for cancer. The journal publishes original laboratory and clinical research papers, case reports and review articles. Publication topics include RNAi approaches, drug resistance, hematopoietic progenitor cell gene transfer, cancer stem cells, cellular therapies, homologous recombination, ribozyme technology, antisense technology, tumor immunotherapy and tumor suppressors, translational research, cancer therapy, gene delivery systems (viral and non-viral), anti-gene therapy (antisense, siRNA & ribozymes), apoptosis; mechanisms and therapies, vaccine development, immunology and immunotherapy, DNA synthesis and repair. Cancer Gene Therapy publishes the results of laboratory investigations, preclinical studies, and clinical trials in the field of gene transfer/gene therapy and cellular therapies as applied to cancer research. Types of articles published include original research articles; case reports; brief communications; review articles in the main fields of drug resistance/sensitivity, gene therapy, cellular therapy, tumor suppressor and anti-oncogene therapy, cytokine/tumor immunotherapy, etc.; industry perspectives; and letters to the editor.
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