The discovery of clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR-Cas9) technology has brought advances in the genetic manipulation of eukaryotic cells, which has revolutionised cancer research and treatment options. It is increasingly being used in cancer immunotherapy, including adoptive T and natural killer (NK) cell transfer, secretion of antibodies, cytokine stimulation and overcoming immune checkpoints. CRISPR-Cas9 technology is used in autologous T cells and NK cells to express various innovative antigen designs and combinations of chimeric antigen receptors (CARs) targeted at specific antigens for haematological and solid tumors. Additionally, advanced engineering in immune cells to enhance their sensing circuits with sophisticated functionality is now possible. Intensive research on the CRISPR-Cas9 system has provided scientists with the ability to overcome the hostile tumor microenvironment and generate more products for future clinical use, especially off-the-shelf, universal cellular products, bringing exciting milestones for immunotherapy. This review discussed the application and challenges of CRISPR technology in cancer research and immunotherapy, its advances and prospects for promoting new cell-based therapeutic beyond immune oncology.

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利用 CRISPR-Cas9 基因编辑系统进行人类癌症和免疫治疗

成簇规律间隔的短回文重复序列和 CRISPR 相关蛋白 9 (CRISPR-Cas9) 技术的发现带来了真核细胞遗传操作的进步，彻底改变了癌症研究和治疗方案。它越来越多地用于癌症免疫治疗，包括过继性 T 细胞和自然杀伤 (NK) 细胞转移、抗体分泌、细胞因子刺激和克服免疫检查点。CRISPR-Cas9技术用于自体T细胞和NK细胞，以表达针对血液学和实体瘤特定抗原的各种创新抗原设计和嵌合抗原受体（CAR）组合。此外，现在可以对免疫细胞进行先进的工程设计，以增强其传感电路的复杂功能。对CRISPR-Cas9系统的深入研究为科学家提供了克服恶劣肿瘤微环境的能力，并产生更多用于未来临床使用的产品，特别是现成的通用细胞产品，为免疫治疗带来了令人兴奋的里程碑。本综述讨论了 CRISPR 技术在癌症研究和免疫治疗中的应用和挑战、其进展以及在免疫肿瘤学之外推广新的基于细胞的治疗的前景。