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恶性胶质瘤患者 CAR-T 细胞疗法的未来发展

英文原题:Future development of chimeric antigen receptor T cell therapies for patients suffering from malignant glioma.

查看英文原题

Future development of chimeric antigen receptor T cell therapies for patients suffering from malignant glioma.

PubMed 2022/07/19(内容时间) Curr Opin Oncol Q3 · IF 2.4(JCR 2025)

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中文摘要

综述目的:CAR-T 细胞疗法已成功治疗部分血液系统恶性肿瘤,但中枢神经系统(CNS)具有独特障碍,限制其用于CNS肿瘤。本文讨论近期细胞递送和设计方面的改进,以提高该疗法治疗恶性胶质瘤的疗效与安全性。 近期发现:CNS免疫抑制环境会影响CAR-T 功能,但代谢调节和细胞因子递送等新进展可改善其表现。新技术可改善CAR-T 递送至CNS实质;该区域通常受到保护,不易被外周免疫细胞进入。新型抗原和CAR表达调控策略可提升细胞特异性和疗效。尽管自体T细胞长期以来是标准选择,近期进展也使异基因T细胞或自然杀伤(NK)细胞的临床应用更可行。 总结:本文所述发现有助于开发更安全、更能抵抗CNS免疫抑制信号且可特异靶向颅内肿瘤细胞的CAR细胞。

展开英文摘要原文

PURPOSE OF REVIEW: 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.

RECENT FINDINGS: 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. SUMMARY: 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.

论文信息

作者
Watchmaker PB、Colton M、Pineo-Cavanaugh PL、Okada H
单位
Department of Neurosurgery, University of California, San Francisco.United States
文献类型
综述 · 美国 NIH 资助研究
期刊
Current opinion in oncology2022 Nov 1
原文标识
PubMed 35855503 · DOI 10.1097/CCO.0000000000000877