Chimeric antigen receptor (CAR) cell therapy has achieved groundbreaking success in treating hematological malignancies. However, its application to solid tumors remains challenging due to complex manufacturing processes, limited in vivo persistence, and transient therapeutic effects. In vivo CAR-immune cells induced by gene delivery systems loaded with CAR genes and gene-editing tools have shown efficiency for anti-tumor immunotherapy. In situ programming of autologous immune cells avoids the safety concerns of allogeneic immune cells, and the manufacture of gene delivery systems could be standardized. Therefore, the in vivo editing and in situ generation of CAR-immune cells might potentially overcome the abovementioned limitations of current CAR cell therapy. This review mainly focuses on CAR structures, gene-editing tools, and gene delivery techniques applied in anti-tumor immunotherapy to help design and develop in situ CAR-immune cell therapy. The recent applications of in vivo CAR-immune cell therapy in both hematologic malignancies and solid tumors are investigated. To sum up, the in vivo editing and in situ generation of CAR therapy holds promise for offering a practical, cost-effective, efficient, safe, and widely applicable approach to the next-generation anti-tumor immunotherapy.

中文翻译：

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用于下一代癌症免疫治疗的体内基因编辑和嵌合抗原受体细胞的原位生成


嵌合抗原受体 （CAR） 细胞疗法在治疗血液系统恶性肿瘤方面取得了突破性的成功。然而，由于复杂的制造工艺、有限的体内持久性和短暂的治疗效果，它在实体瘤中的应用仍然具有挑战性。由载有 CAR 基因和基因编辑工具的基因递送系统诱导的体内 CAR 免疫细胞已显示出抗肿瘤免疫治疗的有效性。自体免疫细胞的原位编程避免了同种异体免疫细胞的安全问题，并且基因递送系统的制造可以标准化。因此，CAR 免疫细胞的体内编辑和原位生成可能会克服当前 CAR 细胞疗法的上述局限性。本文主要关注 CAR 结构、基因编辑工具和基因递送技术在抗肿瘤免疫治疗中的应用，以帮助设计和开发原位 CAR 免疫细胞疗法。研究了体内 CAR 免疫细胞疗法在血液系统恶性肿瘤和实体瘤中的最新应用。综上所述，CAR 疗法的体内编辑和原位生成有望为下一代抗肿瘤免疫疗法提供一种实用、经济高效、安全且广泛适用的方法。