嵌合抗原受体 (CAR) T 细胞疗法:利用细胞外囊泡提高疗效。
CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY: HARNESSING EXTRACELLULAR VESICLES FOR ENHANCED EFFICACY.
发表日期:2024 Aug 13
作者:
Beatrice Spokeviciute, Sharad Kholia, Maria Felice Brizzi
来源:
PHARMACOLOGICAL RESEARCH
摘要:
对抗耐药性癌症的细胞免疫疗法的前沿方法涉及基因工程嵌合抗原受体 T (CAR-T) 淋巴细胞。近年来,这些疗法已被证明有效,从而使其商业化并应用于针对某些类型癌症的临床应用。然而,CAR-T 疗法面临局限性,例如免疫抑制性肿瘤微环境 (TME) 可能导致 CAR-T 细胞无效,以及治疗的不良副作用,包括细胞因子释放综合征 (CRS)。细胞外囊泡 (EV) 是几乎所有细胞类型都释放到细胞外环境中的一组不同的膜结合颗粒。它们对于细胞间通讯、将蛋白质、脂质、各种类型的 RNA 和 DNA 片段等货物转移到靶细胞、穿越局部和全身的生物屏障至关重要。 EV 在许多生理过程中发挥作用,来自免疫和非免疫细胞的 EV 能够通过激活或抑制来调节免疫系统。利用 EV 的这种能力来增强 CAR-T 细胞疗法可能代表着克服其当前局限性的重大进步。本综述探讨了 CAR-T 细胞免疫疗法的现状,并探讨了 EV 在增强其治疗功效方面的潜在作用。版权所有 © 2024。由 Elsevier Ltd 出版。
A cutting-edge approach in cell-based immunotherapy for combating resistant cancer involves genetically engineered chimeric antigen receptor T (CAR-T) lymphocytes. In recent years, these therapies have demonstrated effectiveness, leading to their commercialization and clinical application against certain types of cancer. However, CAR-T therapy faces limitations, such as the immunosuppressive tumour microenvironment (TME) that can render CAR-T cells ineffective, and the adverse side effects of the therapy, including cytokine release syndrome (CRS). Extracellular vesicles (EVs) are a diverse group of membrane-bound particles released into the extracellular environment by virtually all cell types. They are essential for intercellular communication, transferring cargoes such as proteins, lipids, various types of RNAs, and DNA fragments to target cells, traversing biological barriers both locally and systemically. EVs play roles in numerous physiological processes, with those from both immune and non-immune cells capable of modulating the immune system through activation or suppression. Leveraging this capability of EVs to enhance CAR-T cell therapy could represent a significant advancement in overcoming its current limitations. This review examines the current landscape of CAR-T cell immunotherapy and explores the potential role of EVs in augmenting its therapeutic efficacy.Copyright © 2024. Published by Elsevier Ltd.