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:Solid tumour cellular therapy - principles of toxicity management.
Solid tumour cellular therapy - principles of toxicity management.
继美国食品药品监督管理局(FDA)分别批准lifileucel和afami-cel用于晚期黑色素瘤和滑膜肉瘤患者之后,对于实体瘤过继性细胞疗法(ACTs)相关毒性的管理,需要增进理解并提供指导。
美国食品药品监督管理局分别批准lifileucel用于晚期黑色素瘤、afami-cel用于滑膜肉瘤后,临床亟需更充分认识并规范管理实体瘤过继细胞治疗(ACT)相关毒性。预计未来几年还将有更多疗法获批;对计划实施这类先进治疗产品的中心而言,毒性管理是重要考量。重要的是,与CAR-T 细胞和T细胞受体工程化治疗(TCR-T)等基因修饰T细胞疗法相比,第一代TIL(肿瘤浸润淋巴细胞)疗法具有独特毒性,给临床医务人员带来了新的挑战。血液肿瘤领域CAR-T治疗经验、实体瘤治疗方案中既往应用大剂量白细胞介素2的经验,以及近期使用lifileucel和afami-cel的经验,共同推动了ACT毒性管理核心原则的形成,本文对此进行讨论。展望未来,随着新一代ACT产品快速发展,掌握这些核心原则将成为相关医务人员开展工作的基础。
Following the Food and Drug Administration (FDA) approval of lifileucel and afami-cel for patients with advanced melanoma and synovial sarcoma, respectively, there is a need for improved understanding and guidance regarding the management of toxicity associated with adoptive cellular therapies (ACTs) for solid tumours. Further approvals are expected in coming years, with toxicity management representing a significant consideration for centres looking to implement such advanced therapy medicinal products. Importantly, first-generation tumour-infiltrating lymphocyte therapies are associated with unique toxicities compared with gene-modified T-cell therapies such as chimeric antigen receptor T-cell therapy (CAR T) and T-cell receptor-modified therapy (TCR T), presenting novel challenges for treating healthcare professionals. Extrapolating from experience with CAR T in the field of haemato-oncology, coupled with the historical use of high-dose interleukin-2 in solid tumour therapeutic regimens and more recently lifileucel and afami-cel, has led to the development of core principles for managing toxicity, which is discussed here. Looking to the future, a rapidly developing field with next-generation ACT products, a basic knowledge of such core principles will be an important foundation for healthcare professionals working in this space.
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