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放疗与 CAR-T 的高效联合:一项系统综述

英文原题:Efficient combination of radiotherapy and CAR-T - A systematic review.

查看英文原题

Efficient combination of radiotherapy and CAR-T - A systematic review.

PubMed 2024/04/03(内容时间) Biomed Pharmacother

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中文摘要

CAR-T(CAR-T)细胞疗法是一种突破性免疫疗法,但治疗实体瘤仍面临重大挑战,包括向肿瘤微环境(TME)迁移不足、穿透受限以及持久性不足。CAR-T 细胞经工程化改造表达靶向特定癌症抗原的受体,从而增强识别和清除癌细胞的能力。本文探讨CAR-T 疗法与放疗(RT)之间的复杂相互作用及其协同潜力。放疗是标准癌症治疗方法,通过高剂量辐射靶向并损伤癌细胞,阻止其生长和分裂。本文强调,RT可调节TME、增强抗原呈递并促进免疫细胞浸润,从而加强CAR-T 细胞介导的肿瘤清除。分子层面的研究揭示了RT诱导的肿瘤基质改变、促进T细胞募集及诱导免疫原性细胞死亡等机制。值得关注的是,将低分割放疗与髓源性抑制细胞阻断相结合等策略,为增强CAR-T 治疗实体瘤提供了创新方向。文章还讨论血液系统恶性肿瘤中RT与CAR-T 的桥接适应证,重点说明RT可策略性增强CAR-T 疗效的情境。本文批判性评估将RT作为桥接治疗与传统化疗相比的作用,并强调优化CAR-T 治疗结局所需的关键时序和剂量考量。

总之,本文为理解RT激活的复杂分子机制及改善CAR-T 疗法的创新策略提供了有价值见解,深化了对二者联合治疗癌症潜力的认识。

展开英文摘要原文

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking immunotherapy.

However, it faces formidable challenges in treating solid tumors, grappling with issues like poor trafficking, limited penetration, and insufficient persistence within the tumor microenvironment (TME). CAR-T cells are engineered to express receptors that target specific cancer antigens, enhancing their ability to recognize and eliminate cancer cells.

This review paper explores the intricate interplay between CAR-T therapy and radiotherapy (RT), investigating their synergistic potential. Radiotherapy, a standard cancer treatment, involves using high doses of radiation to target and damage cancer cells, disrupting their ability to grow and divide.

We highlight that RT modulates the TME, augments antigen presentation, and promotes immune cell infiltration, bolstering CAR-T cell-mediated tumor eradication. Molecular insights shed light on RT-induced alterations in tumor stroma, T cell recruitment promotion, and induction of immunogenic cell death. Noteworthy, strategies, such as combining hypofractionated radiotherapy with myeloid-derived suppressor cell blockade, underscore innovative approaches to enhance CAR-T cell therapy in solid tumors.

Bridging indications for RT and CAR-T cells in hematological malignancies are discussed, emphasizing scenarios where RT strategically enhances CAR-T cell efficacy. The paper critically evaluates the RT as a bridge compared to traditional chemotherapy, highlighting timing and dosage considerations crucial for optimizing CAR-T therapy outcomes.

In summary, the paper provides valuable insights into the intricate molecular mechanisms activated by RT and innovative strategies to improve CAR-T cell therapy, fostering a deeper understanding of their combined potential in cancer treatment.

论文信息

作者
Szlasa W、Sztuder A、Kaczmar-Dybko A、Maciejczyk A、Dybko J
单位
Lower Silesian Centre of Oncology, Pulmonology and Hematology, Wroclaw 53-413, Poland; Medical University Hospital, Borowska 213, Wrocław 50-556, Poland. Electronic address: wojtek.szlasa@gmail.com.Poland
文献类型
系统综述
期刊
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2024 May
原文标识
PubMed 38574625 · DOI 10.1016/j.biopha.2024.116532