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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
改善 CAR-T 免疫治疗：克服 T 细胞耗竭的挑战
英文原题：Improving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion.
查看英文原题
Improving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion.
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中文摘要
嵌合抗原受体（CAR）T细胞疗法已成为一种具有巨大潜力的癌症治疗方法，在血液系统恶性肿瘤的治疗中展现出显著的抗肿瘤活性。然而，CAR-T 细胞耗竭是其疗效的主要限制因素，尤其是在CAR-T 细胞应用于实体瘤时。CAR-T 细胞耗竭被认为是由持续性抗原刺激以及免疫抑制性肿瘤微环境所致，而减轻耗竭以维持CAR-T 细胞效应功能和持久性并实现临床效力仍是一项核心挑战。在此，我们综述了耗竭的潜在机制，并讨论了通过修饰CAR受体或CAR非依赖性通路来预防或逆转耗竭的新兴策略。此外，我们还讨论了这些策略在改善CAR-T 细胞治疗临床结局方面的潜力。
展开英文摘要原文
Chimeric antigen receptor (CAR) T cell therapy has emerged as a cancer treatment with enormous potential, demonstrating impressive antitumor activity in the treatment of hematological malignancies.
However, CAR T cell exhaustion is a major limitation to their efficacy, particularly in the application of CAR T cells to solid tumors. CAR T cell exhaustion is thought to be due to persistent antigen stimulation, as well as an immunosuppressive tumor microenvironment, and mitigating exhaustion to maintain CAR T cell effector function and persistence and achieve clinical potency remains a central challenge.
Here, we review the underlying mechanisms of exhaustion and discuss emerging strategies to prevent or reverse exhaustion through modifications of the CAR receptor or CAR independent pathways.
Additionally, we discuss the potential of these strategies for improving clinical outcomes of CAR T cell therapy.
论文信息
- 作者
- Gumber D、Wang LD
- 第一作者单位
- Irell and Manella Graduate School of Biological Sciences, City of Hope National Medical Center, Beckman Research Institute, Duarte CA, United States; Department of Immunooncology, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, United States.United States
- 通讯作者单位
- Irell and Manella Graduate School of Biological Sciences, City of Hope National Medical Center, Beckman Research Institute, Duarte CA, United States; Department of Immunooncology, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, United States; Department of Pediatrics, City of Hope National Medical Center, Duarte, CA, United States. Electronic address: leo.wang@coh.org.United States
- 文献类型
- 综述
- 期刊
- EBioMedicine2022 Mar
- 原文标识
- PubMed 35301179 · DOI 10.1016/j.ebiom.2022.103941
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