College of Biotechnology, Southwest University, Chongqing, 400715, China.
State Key Laboratory of Trauma, Burn and Combined Injury, Department of Stem Cell & Regenerative Medicine, Daping Hospital and Research Institute of Surgery, Chongqing, 400042, China.
Front Med. 2020 Dec;14(6):726-745. doi: 10.1007/s11684-020-0746-0. Epub 2020 Aug 13.
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.
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方面非常有效，并在临床前和临床试验中取得了令人鼓舞的结果。然而，由于 CAR T 细胞向肿瘤的迁移不足、扩增和持续存在不良以及抗原阴性复发和免疫抑制微环境等额外障碍，CAR T 细胞在治疗实体恶性肿瘤方面取得的成功甚微。各种临床前研究正在探索克服上述挑战的策略。鉴于先天免疫反应在消除恶性肿瘤中的重要性，为了使 CAR T 细胞获得最佳治疗效果，还需要动员内源性免疫细胞。在这篇综述中，我们重点介绍了 CAR T 细胞疗法在恢复实体恶性肿瘤免疫反应方面的最新进展，特别是 CAR T 细胞作为细胞载体将免疫调节剂递送到肿瘤中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 细胞治疗的致敏作用。最后，我们讨论了 CAR T 细胞与生物材料或溶瘤病毒的联合使用，以增强 CAR T 细胞疗法在实体肿瘤中的抗肿瘤效果。
