CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CAR-T 细胞耗竭：潜在原因与解决方案
英文原题：Exhaustion of CAR T cells: potential causes and solutions.
查看英文原题
Exhaustion of CAR T cells: potential causes and solutions.
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中文摘要
嵌合抗原受体（CAR）T细胞疗法因其治疗血液系统恶性肿瘤的良好疗效而备受关注。然而，该疗法仍存在长期随访中复发以及对实体瘤效果有限等问题。耗竭会损害CAR-T 细胞体内持续存在能力和杀伤活性，是导致这些问题的原因之一。根据胞外部分结构，某些CAR在没有配体刺激时也会诱导基础性信号，并使CAR-T 细胞形成耗竭表型。分析这类自激活CAR有望为理解和解决CAR-T 细胞耗竭提供关键信息。本文介绍自激活CAR的实例并总结其表型，以厘清CAR-T 细胞耗竭的发生机制；还综述克服CAR-T 细胞耗竭、促进其广泛应用的有前景方案。
展开英文摘要原文
Chimeric antigen receptor (CAR) T cell therapy has attracted attention for its promising therapeutic effects on hematological malignancies.
However, there are problems such as relapse during long-term follow-up and limited effect on solid tumors with this therapy. Exhaustion, which impairs in vivo persistence and killing activity of CAR T cells, is one of the causes of these issues. Depending on their structure of extracellular portion, some CARs induce tonic signals in the absence of ligand stimulation and induce exhaustion phenotype in CAR T cells.
Analysis of these self-activating CARs is expected to provide key information for understanding and resolving CAR T cell exhaustion. In this review, we introduced examples of self-activating CARs and summarized their phenotypes to figure out how CAR T cell exhaustion occurs.
Further, we aimed to review promising solutions to the CAR T cell exhaustion that hampers generalized application of CAR T cell therapy.
论文信息
- 作者
- Kouro T、Himuro H、Sasada T
- 单位
- Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama, Japan. kourot@gancen.asahi.yokohama.jp.Japan
- 文献类型
- 综述 · 非美国政府资助研究
- 期刊
- Journal of translational medicine2022 May 23
- 原文标识
- PubMed 35606821 · DOI 10.1186/s12967-022-03442-3
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