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
英文原题:CAR-T-Derived Extracellular Vesicles: A Promising Development of CAR-T Anti-Tumor Therapy.
CAR-T-Derived Extracellular Vesicles: A Promising Development of CAR-T Anti-Tumor Therapy.
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细胞外囊泡(EV)是由几乎所有类型的活细胞释放至细胞外环境的一类异质性颗粒,外有质膜包裹。EV能够将蛋白质、脂质、mRNA、miRNA和DNA片段等载荷递送至靶细胞,并跨越生物屏障,因此在局部及全身细胞间通讯中发挥关键作用;这些过程可进一步触发广泛的生物学应答。有趣的是,EV的表型和载荷,以及由此产生的功能,取决于其来源细胞。
因此,EV已被视为开发基于EV的无细胞疗法的有前景候选物。针对难治性肿瘤疾病的细胞免疫疗法领域中一个新的前沿方向,是基因工程化CAR-T(CAR-T)淋巴细胞。近年来,CAR-T 疗法已显示有效,并在部分肿瘤疾病中实现商业化和临床应用。CAR-T 来源EV是CAR-T 免疫疗法中一种新近且有前景的发展方向。这种跨领域创新策略旨在结合基因工程细胞免疫疗法与无细胞EV的优势;原则上,后者可能具有更高安全性,并能更有效地穿越生物屏障及肿瘤相关屏障。本综述强调CAR-T 来源EV作为肿瘤治疗药物的潜力。
Extracellular vesicles (EVs) are a heterogenous population of plasma membrane-surrounded particles that are released in the extracellular milieu by almost all types of living cells. EVs are key players in intercellular crosstalk, both locally and systemically, given that they deliver their cargoes (consisting of proteins, lipids, mRNAs, miRNAs, and DNA fragments) to target cells, crossing biological barriers. Those mechanisms further trigger a wide range of biological responses. Interestingly, EV phenotypes and cargoes and, therefore, their functions, stem from their specific parental cells. For these reasons, EVs have been proposed as promising candidates for EV-based, cell-free therapies.
One of the new frontiers of cell-based immunotherapy for the fight against refractory neoplastic diseases is represented by genetically engineered chimeric antigen receptor T (CAR-T) lymphocytes, which in recent years have demonstrated their effectiveness by reaching commercialization and clinical application for some neoplastic diseases. CAR-T-derived EVs represent a recent promising development of CAR-T immunotherapy approaches.
This crosscutting innovative strategy is designed to exploit the advantages of genetically engineered cell-based immunotherapy together with those of cell-free EVs, which in principle might be safer and more efficient in crossing biological and tumor-associated barriers. In this review, we underlined the potential of CAR-T-derived EVs as therapeutic agents in tumors.
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