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:Challenges and new technologies in adoptive cell therapy.
Challenges and new technologies in adoptive cell therapy.
过继性细胞疗法(ACTs)已存在数十年。
过继性细胞疗法(ACT)已有数十年历史。从最初输注TIL(肿瘤浸润淋巴细胞),到后续特异性增强的 T 细胞受体(TCR)T 细胞疗法和嵌合抗原受体(CAR)T 细胞疗法,研究人员已开发出多种肿瘤治疗新策略。CAR-T 细胞疗法取得的良好疗效推动了 ACT 领域的变革,尤其是在血液系统恶性肿瘤中。尽管取得这些进展,CAR-T 细胞疗法在自体和异体应用中仍存在实际操作和毒性方面的局限。为克服这些挑战,研究者开始将 CAR 工程化技术用于其他类型免疫细胞的改造,由此开发出多种 CAR 技术衍生的细胞疗法,包括 CAR-NK、CAR-巨噬细胞、CAR-γδ T 细胞和 CAR-NKT。本文综述了上述 ACT 的发展、优势和潜在挑战,并讨论了旨在最大化 ACT 治疗潜力的现行策略。鉴于基因导入策略对免疫细胞工程的重要性,本文还概述了免疫疗法中使用的各种基因转导方法。此外,我们探讨了能够建立正向反馈免疫回路(类似健康免疫系统)的策略是否可以弥补单一类型 ACT 的缺陷,并成为未来癌症免疫治疗的关键方向。
Adoptive cell therapies (ACTs) have existed for decades. From the initial infusion of tumor-infiltrating lymphocytes to the subsequent specific enhanced T cell receptor (TCR)-T and chimeric antigen receptor (CAR)-T cell therapies, many novel strategies for cancer treatment have been developed. Owing to its promising outcomes, CAR-T cell therapy has revolutionized the field of ACTs, particularly for hematologic malignancies. Despite these advances, CAR-T cell therapy still has limitations in both autologous and allogeneic settings, including practicality and toxicity issues. To overcome these challenges, researchers have focused on the application of CAR engineering technology to other types of immune cell engineering. Consequently, several new cell therapies based on CAR technology have been developed, including CAR-NK, CAR-macrophage, CAR- T, and CAR-NKT. In this review, we describe the development, advantages, and possible challenges of the aforementioned ACTs and discuss current strategies aimed at maximizing the therapeutic potential of ACTs. We also provide an overview of the various gene transduction strategies employed in immunotherapy given their importance in immune cell engineering. Furthermore, we discuss the possibility that strategies capable of creating a positive feedback immune circuit, as healthy immune systems do, could address the flaw of a single type of ACT, and thus serve as key players in future cancer immunotherapy.
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