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:CAR-T Cell Therapy for Classical Hodgkin Lymphoma.
经典型霍奇金淋巴瘤(cHL)是一种以复杂肿瘤微环境(TME)中存在霍奇金和 Reed-Sternberg(HRS)细胞为特征的恶性肿瘤。
经典型霍奇金淋巴瘤(cHL)是一种恶性肿瘤,其特征为复杂肿瘤微环境(TME)中存在霍奇金-里德-斯滕伯格(HRS)细胞。尽管传统疗法有所进步,部分cHL患者仍会复发或出现难治性疾病,因此需要探索新的治疗策略。CAR-T 细胞疗法是一种有前景的cHL治疗方法,利用经基因改造的T细胞识别并清除肿瘤细胞。本文概述cHL发病机制及相关关键分子和细胞机制,并讨论开发cHL CAR-T疗法的依据,重点介绍CAR设计中可用的靶点,包括HRS细胞上的CD30、CD123、LMP1和LMP2A,克隆型淋巴瘤起始B细胞上的CD19和CD20,以及TME内细胞上的CD123、CD19和CD20。本文还探讨提高cHL CAR-T疗效和安全性的各种策略,并概述评估cHL CAR-T疗效的临床试验结果,强调其作为有前景治疗选择的潜力。总之,本文全面回顾了当前对cHL发病机制及CAR-T开发依据的认识,并展望这一快速发展的领域未来方向。
Classical Hodgkin lymphoma (cHL) is a malignancy characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells within a complex tumor microenvironment (TME). Despite advances in conventional therapies, a subset of cHL patients experience relapse or refractory disease, necessitating the exploration of novel treatment strategies. Chimeric antigen receptor T cell (CAR-T cell) therapy has emerged as a promising approach for the management of cHL, harnessing the power of genetically modified T cells to recognize and eliminate tumor cells. In this article, we provide an overview of the pathogenesis of cHL, highlighting the key molecular and cellular mechanisms involved. Additionally, we discuss the rationale for the development of CAR-T cell therapy in cHL, focusing on the identification of suitable targets on HRS cells (such as CD30, CD123, LMP1, and LMP2A), clonotypic lymphoma initiating B cells (CD19, CD20), and cells within the TME (CD123, CD19, CD20) for CAR-T cell design. Furthermore, we explore various strategies employed to enhance the efficacy and safety of CAR-T cell therapies in the treatment of cHL. Finally, we present an overview of the results obtained from clinical trials evaluating the efficacy of CAR-T cell therapies in cHL, highlighting their potential as a promising therapeutic option. Collectively, this article provides a comprehensive review of the current understanding of cHL pathogenesis and the rationale for CAR-T cell therapy development, offering insights into the future directions of this rapidly evolving field.
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