决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:From concept to cure: The evolution of CAR-T cell therapy.
嵌合抗原受体(CAR)-T细胞疗法在21世纪彻底改变了癌症免疫治疗,为以前无法治疗的疾病提供了创新的解决方案和救生疗法。
嵌合抗原受体(CAR)-T 细胞疗法在 21 世纪彻底改变了肿瘤免疫治疗,为既往无法治疗的疾病提供了创新解决方案和挽救生命的疗法。该方法在治疗多种血液系统恶性肿瘤方面已取得显著成功,目前正扩展至实体瘤(如前列腺癌和胶质母细胞瘤)以及感染性疾病和自身免疫性疾病的临床试验中。CAR-T 细胞疗法包括采集患者的 T 细胞,利用病毒载体对其进行基因工程改造,使其表达靶向特定抗原的 CAR,并将改造后的细胞回输给患者。这些 CAR-T 细胞的功能不依赖于主要组织相容性复合体(MHC)的抗原提呈,能够选择性识别并清除靶细胞。本综述重点阐述 CAR-T 细胞从发明到临床应用的演变过程中的关键里程碑,概述了导致 CAR-T 细胞发明的历史时间线,讨论了使其成为突破性疗法的重大成就,并探讨了尚存的挑战,包括高昂的生产成本、可及性有限,以及细胞因子释放综合征和免疫效应细胞相关神经毒性综合征等毒性问题。此外,本综述还探讨了该领域的未来方向与进展,例如开发旨在最大化疗效、最小化毒性并拓宽治疗应用的下一代 CAR-T 细胞。
Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer immunotherapy in the 21st century, providing innovative solutions and life-saving therapies for previously untreatable diseases. This approach has shown remarkable success in treating various hematological malignancies and is now expanding into clinical trials for solid tumors, such as prostate cancer and glioblastoma, as well as infectious and autoimmune diseases. CAR-T cell therapy involves harvesting a patient's T cells, genetically engineering them with viral vectors to express CARs targeting specific antigens and reinfusing the modified cells into the patient. These CAR-T cells function independently of major histocompatibility complex (MHC) antigen presentation, selectively identifying and eliminating target cells. This review highlights the key milestones in CAR-T cell evolution, from its invention to its clinical applications. It outlines the historical timeline leading to the invention of CAR-T cells, discusses the major achievements that have transformed them into a breakthrough therapy, and addresses remaining challenges, including high manufacturing costs, limited accessibility, and toxicity issues such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Additionally, the review explores future directions and advances in the field, such as developing next-generation CAR-T cells aiming to maximize efficacy, minimize toxicity, and broaden therapeutic applications.
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