Department of Neurosurgery, University of California, San Francisco.
Parker Institute for Cancer Immunotherapy, San Francisco, California, USA.
Curr Opin Oncol. 2022 Nov 1;34(6):661-669. doi: 10.1097/CCO.0000000000000877. Epub 2022 Jul 19.
Chimeric antigen receptor (CAR) T cell therapy has been successful in some haematologic malignancies, but the central nervous system (CNS) presents unique obstacles to its use against tumours arising therein. This review discusses recent improvements in the delivery and design of these cells to improve the efficacy and safety of this treatment against malignant gliomas.
The immunosuppressive environment of the CNS affects the functionality of CAR T cells, but recent developments using metabolic manipulation and cytokine delivery have shown that the performance of CAR T cells can be improved in this environment. Emerging techniques can improve the delivery of CAR T cells to the CNS parenchyma, which is normally well protected from peripheral immune cells. The implementation of novel antigens and CAR-expression regulation strategies will improve the specificity and efficacy of these cells. Finally, although autologous T cells have historically been the standard, recent developments have made the use of allogeneic T cells or natural killer (NK) cells more clinically feasible.
The discoveries highlighted in this review will aid the development of CAR cells that are safer, more resilient against immunosuppressive signals in the CNS, and able to specifically target intracranial tumour cells.
嵌合抗原受体（CAR）T 细胞疗法在某些血液恶性肿瘤中取得了成功，但中枢神经系统（CNS）对其用于治疗源自其中的肿瘤存在独特的障碍。本综述讨论了这些细胞的传递和设计的最新进展，以提高该治疗方法对恶性神经胶质瘤的疗效和安全性。
CNS 的免疫抑制环境会影响 CAR T 细胞的功能，但最近使用代谢操纵和细胞因子传递的研究表明，CAR T 细胞在这种环境下的性能可以得到改善。新兴技术可以改善 CAR T 细胞向 CNS 实质的传递，而 CNS 实质通常可以很好地免受外周免疫细胞的影响。新型抗原和 CAR 表达调控策略的实施将提高这些细胞的特异性和疗效。最后，尽管自体 T 细胞一直是标准，但最近的研究进展使得同种异体 T 细胞或自然杀伤（NK）细胞的使用在临床上更可行。
本综述强调的发现将有助于开发更安全、对 CNS 中的免疫抑制信号更有抵抗力、能够特异性靶向颅内肿瘤细胞的 CAR 细胞。
