利用CRISPR/Cas9优化过继性T细胞疗法：从分子工程到临床生产
Leveraging CRISPR/Cas9 for optimized adoptive T cell therapies: From molecular engineering to clinical manufacturing.
摘要(中文译文)
癌症免疫治疗正迅速从药物性免疫调节向过继性细胞治疗（ACT）演进。在ACT中，T细胞在体外扩增并进行基因工程改造，以获得持久的抗肿瘤活性。主要的ACT平台——肿瘤浸润淋巴细胞（TIL）、嵌合抗原受体（CAR）T细胞和T细胞受体（TCR）T细胞——均依赖T细胞效应功能，但在抗原识别机制、HLA依赖性及工程化改造需求方面各不相同，因而具有各自独特的临床优势和局限性。CRISPR/Cas9基因组编辑提供了精确的敲除（KO）和敲入（KI）策略，可实现全基因组范围内的多重编辑和功能调控。在ACT生产制造背景下，CRISPR/Cas9可解决T细胞耗竭、移植物抗宿主病（GvHD）以及确保产品一致性和质量等关键挑战。本文探讨如何利用CRISPR/Cas9克服ACT的局限性，并总结CRISPR工程化ACT产品的当前临床格局。最后，我们讨论基于CRISPR的基因组编辑所面临的持续挑战，并提出潜在解决方案。
Abstract
Cancer immunotherapy is rapidly evolving from pharmacologic immune modulation to adoptive cell therapy (ACT). In ACT, T cells are expanded and genetically engineered ex vivo to achieve long-lasting antitumor activity. The primary ACT platforms-tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR) T cells, and T-cell receptor (TCR) T cells-rely on T-cell effector function but differ in their mechanisms of antigen recognition, HLA dependence, and engineering requirements, leading to unique clinical strengths and limitations. CRISPR/Cas9 genome editing provides precise knock-out (KO) and knock-in (KI) strategies, allowing for multiplex editing and functional modulation across the genome. In the context of ACT manufacturing, CRISPR/Cas9 addresses critical challenges such as T-cell exhaustion, graft-versus-host disease (GvHD), and ensuring product consistency and quality. This article explores how CRISPR/Cas9 can be utilized to overcome the limitations of ACT and summarizes the current clinical landscape of CRISPR-engineered ACT products. Finally, we discuss the ongoing challenges associated with CRISPR-based genome editing and propose potential solutions.
如何引用
AMA
Ji-Hyeon Kim, Hyo Jung Cho, Hyang-Mi Lee. Leveraging CRISPR/Cas9 for optimized adoptive T cell therapies: From molecular engineering to clinical manufacturing.. Biochemical and biophysical research communications. 2026; doi:10.1016/j.bbrc.2026.154003.
APA
Ji-Hyeon Kim, Hyo Jung Cho, Hyang-Mi Lee (2026). Leveraging CRISPR/Cas9 for optimized adoptive T cell therapies: From molecular engineering to clinical manufacturing.. Biochemical and biophysical research communications. https://doi.org/10.1016/j.bbrc.2026.154003
GB/T 7714
Ji-Hyeon Kim, Hyo Jung Cho, Hyang-Mi Lee. Leveraging CRISPR/Cas9 for optimized adoptive T cell therapies: From molecular engineering to clinical manufacturing.[J]. Biochemical and biophysical research communications, 2026 doi:10.1016/j.bbrc.2026.154003.
在 PubMed增强版 阅读全文
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出