Faculdade de Engenharia da Universidade do Porto (FEUP), 4200-465 Porto, Portugal.
Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal.
Int J Mol Sci. 2023 Mar 27;24(7):6300. doi: 10.3390/ijms24076300.
After seeing a dramatic increase in the development and use of immunotherapy and precision medicine over the past few decades, oncological care now embraces the start of the adoptive cell therapy (ACT) era. This impulse towards a new treatment paradigm has been led by chimeric antigen receptor (CAR) T cells, the only type of ACT medicinal product to be commercialized so far. Brought about by an ever-growing understanding of cellular engineering, CAR T cells are T lymphocytes genetically modified with an appropriate DNA construct, which endows them with expression of a CAR, a fusion protein between a ligand-specific recognition domain, often an antibody-like structure, and the activating signaling domain of the T cell receptor. Through this genetic enhancement, CAR T cells are engineered from a cancer patient's own lymphocytes to better target and kill their cancer cells, and the current amassed data on clinical outcomes point to a stream of bright developments in the near future. Herein, from concept design and present-day manufacturing techniques to pressing hurdles and bright discoveries around the corner, we review and thoroughly describe the state of the art in CAR T cell therapy.
在过去几十年中,免疫疗法和精准医学的发展和应用呈显著上升趋势,肿瘤治疗领域目前已进入过继细胞疗法(ACT)时代。这种新的治疗模式的发展动力主要来自嵌合抗原受体(CAR)T 细胞,这是迄今为止唯一一种实现商业化的 ACT 药物。随着对细胞工程的认识不断深入,CAR T 细胞是经过适当 DNA 构建体修饰的 T 淋巴细胞,赋予其 CAR 的表达,CAR 是配体特异性识别域(通常为类似抗体的结构)与 T 细胞受体的激活信号域融合而成的融合蛋白。通过这种基因增强,CAR T 细胞由癌症患者自身的淋巴细胞工程化而来,以更好地靶向和杀死癌细胞,目前积累的临床结果数据表明,在不久的将来将会有一系列的积极进展。在此,我们从概念设计和当前的制造技术到迫在眉睫的障碍和即将到来的重大发现,全面回顾并详细描述了 CAR T 细胞疗法的最新进展。