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:The Art of Bioimmunogenomics (BIGs) 5.0 in CAR-T Cell Therapy for Lymphoma Management.
尽管CAR-T细胞免疫疗法的疗效和安全性仍是热烈研究的课题,但这项前沿技术的前景为淋巴瘤治疗管理方法的未来发展提供了宝贵的见解。此外,CAR-T细胞疗法可能使患者获益,促使监管机构促进国际合作。
淋巴瘤是最主要的肿瘤性疾病,分为霍奇金淋巴瘤和非霍奇金淋巴瘤两类。免疫治疗手段已成为对抗淋巴系统恶性肿瘤的重要方法。嵌合抗原受体(CAR)T细胞在化疗耐药的B细胞非霍奇金淋巴瘤病例中展现出有希望的疗效。
这篇综合综述阐述了CAR-T细胞疗法作为免疫治疗工具的发展、用于CAR-T细胞靶向的淋巴瘤抗原选择,以及CAR-T细胞的概念化、合成和部署。此外,它还涵盖了CAR-T细胞疗法的优势和劣势,以及从计算研究视角看CAR-T细胞的前景。为了改进人工CAR的设计和功能,需要进行TCR识别研究,随后实施质量监测方法。
多种淋巴瘤抗原适合作为CAR-T细胞的靶点,如CD19、CD20、CD22、CD30、κ轻链和ROR1。CAR-T细胞疗法的一个显著优势是增强了免疫系统在化疗耐药淋巴瘤患者中产生杀肿瘤活性的能力。然而,它也带来了制造上的障碍,这些障碍费时费力、技术难度高且经济负担重。物理、物理化学和生理学方面的局限性进一步加剧了CAR-T细胞治疗实体肿瘤的挑战。
PURPOSE: Lymphoma, the most predominant neoplastic disorder, is divided into Hodgkin and Non-Hodgkin Lymphoma classifications. Immunotherapeutic modalities have emerged as essential methodologies in combating lymphoid malignancies. Chimeric Antigen Receptor (CAR) T cells exhibit promising responses in chemotherapy-resistant B-cell non-Hodgkin lymphoma cases. METHODS: This comprehensive review delineates the advancement of CAR-T cell therapy as an immunotherapeutic instrument, the selection of lymphoma antigens for CAR-T cell targeting, and the conceptualization, synthesis, and deployment of CAR-T cells. Furthermore, it encompasses the advantages and disadvantages of CAR-T cell therapy and the prospective horizons of CAR-T cells from a computational research perspective. In order to improve the design and functionality of artificial CARs, there is a need for TCR recognition investigation, followed by the implementation of a quality surveillance methodology. RESULTS: Various lymphoma antigens are amenable to CAR-T cell targeting, such as CD19, CD20, CD22, CD30, the kappa light chain, and ROR1. A notable merit of CAR-T cell therapy is the augmentation of the immune system's capacity to generate tumoricidal activity in patients exhibiting chemotherapy-resistant lymphoma. Nevertheless, it also introduces manufacturing impediments that are laborious, technologically demanding, and financially burdensome. Physical, physicochemical, and physiological limitations further exacerbate the challenge of treating solid neoplasms with CAR-T cells. CONCLUSION: While the efficacy and safety of CAR-T cell immunotherapy remain subjects of fervent investigation, the promise of this cutting-edge technology offers valuable insights for the future evolution of lymphoma treatment management approaches. Moreover, CAR-T cell therapies potentially benefit patients, motivating regulatory bodies to foster international collaboration.
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