免疫细胞治疗中的挑战和新技术。
Challenges and new technologies in adoptive cell therapy.
发表日期:2023 Aug 18
作者:
Pengchao Zhang, Guizhong Zhang, Xiaochun Wan
来源:
BIOMEDICINE & PHARMACOTHERAPY
摘要:
细胞免疫疗法(ACT)已存在数十年。从最初的肿瘤浸润淋巴细胞输注到后来的特异性增强型T细胞受体(TCR-T)和嵌合抗原受体(CAR-T)细胞疗法,许多新的癌症治疗策略已经被开发出来。由于其有希望的疗效,CAR-T细胞疗法已经彻底改变了ACT领域,尤其是用于血液系统恶性肿瘤的治疗。尽管取得了这些进展,CAR-T细胞疗法在自体和异体环境中仍然存在局限性,包括实用性和毒性问题。为了克服这些挑战,研究人员已经开始将CAR工程技术应用于其他类型的免疫细胞工程。因此,已经发展出了几种基于CAR技术的新型细胞疗法,包括CAR-NK、CAR-巨噬细胞、CAR-γδT和CAR-NKT。在本综述中,我们描述了上述ACT的发展、优势和可能面临的挑战,并讨论了目前旨在最大限度发挥ACT治疗潜力的策略。我们还概述了在免疫细胞工程中应用的各种基因转导策略,并探讨了能够创造正反馈免疫回路的策略的可能性,正如健康免疫系统所做的那样,这可能解决单一类型ACT的缺陷,并在未来的癌症免疫疗法中起到关键作用。© 2023. BioMed Central Ltd., part of Springer Nature.
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-γδT, 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.© 2023. BioMed Central Ltd., part of Springer Nature.