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:Optimizing CAR-T therapy in diffuse large B-cell lymphoma: Biological determinants and translational strategies across the therapeutic continuum.
CAR-T 细胞疗法已改变了复发或难治性弥漫性大B细胞淋巴瘤(DLBCL)的治疗格局,但仍有相当一部分患者未能获得持久缓解。
CAR-T 细胞疗法已改变了复发或难治性弥漫大B细胞淋巴瘤(DLBCL)的治疗格局,但仍有相当比例的患者未能获得持久缓解。这些局限性既源于初始应答不足,也源于后续疾病复发。尽管已有多种优化策略可供选择,但其临床实施仍面临挑战,部分原因在于这些策略作用于治疗连续过程中的不同节点,并针对不同的生物学或临床障碍,导致临床实施格局呈现碎片化,缺乏统一框架。在本综述中,我们从临床导向出发,对提高CAR-T在DLBCL中疗效的策略进行综合梳理,聚焦于两个相互关联的目标:提高初始缓解率和维持长期疾病控制。我们讨论了白细胞分离术前、生产过程中、输注前、体内扩增期间以及缓解后的干预措施如何影响临床结局。我们还讨论了体内CAR-T技术作为一种新兴平台,具有拓展治疗格局和提高可及性的潜力。通过整合各项研究的证据,本综述为优化CAR-T在DLBCL中的疗效提供了全面而系统的视角,同时强调了当前证据空白和临床实施面临的挑战。
Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), yet a substantial proportion of patients fail to achieve durable remission. These limitations arise from both inadequate initial response and subsequent disease relapse. Despite the availability of multiple optimization strategies, their clinical implementation remains challenging, partly because these approaches act at different points along the therapeutic continuum and address distinct biological or clinical barriers, resulting in a fragmented clinical implementation landscape that lacks a unified framework. In this review, we provide a clinically oriented synthesis of strategies to improve CAR-T efficacy in DLBCL, focusing on two interconnected objectives: enhancing initial remission and sustaining long-term disease control. We discuss how interventions before leukapheresis, during manufacturing, before infusion, during in vivo expansion, and after remission may shape clinical outcomes. We also discuss in vivo CAR-T technologies as an emerging platform with the potential to expand the therapeutic landscape and improve accessibility. By integrating evidence across studies, this review provides a comprehensive and systematic perspective on optimizing CAR-T efficacy in DLBCL while highlighting current evidence gaps and challenges to clinical implementation.
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