Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system
Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system
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DOI：
10.1007/s11684-020-0746-0
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发表时间：
2020-08
影响因子：
8.1
通讯作者：
Xiaohui Wang;Zhiqiang Wu;W. Qiu;Ping Chen;Xiang Xu;W. Han
中科院分区：
文献类型：
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作者：
Xiaohui Wang;Zhiqiang Wu;W. Qiu;Ping Chen;Xiang Xu;W. Han
嵌合抗原受体（CAR）T细胞已被证明在治疗B细胞急性淋巴细胞白血病和非霍奇金淋巴瘤中有效，并且在临床前和临床研究中显示出令人鼓舞的结果。然而，CAR T细胞在对抗实体恶性肿瘤方面取得的成功微乎其微，这是因为除了抗原阴性复发和免疫抑制微环境之外，它们向肿瘤中的迁移不足以及扩增和持久性差的额外障碍。各种临床前研究正在探索克服上述挑战的策略。鉴于先天免疫应答在消除恶性肿瘤中的重要性，内源性免疫细胞的动员对于CAR T细胞获得其最佳治疗效果也是必要的。在这篇综述中，我们重点介绍了CAR T细胞治疗工程的最新进展，以恢复实体恶性肿瘤的免疫反应，特别是CAR T细胞作为细胞载体向肿瘤提供免疫调节剂以动员内源性免疫反应。我们还探讨了常规治疗方法（如化疗和放疗）对CAR T细胞治疗的增敏作用。最后，我们讨论了CAR T细胞与生物材料或溶瘤病毒的组合，以增强实体瘤中CAR T细胞疗法的抗肿瘤结果。
Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.