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:Clinical trials for chimeric antigen receptor T-cell therapy: lessons learned and future directions.
靶向 CD19 的 CAR-T 细胞治疗(CD19-CAR)对复发/难治性(r/r)B 细胞血液系统恶性肿瘤患者高度有效。
综述目的:根据最新临床试验,总结CAR-T 细胞疗法用于白血病和淋巴瘤患者的现状和应用。此外,本文将突出当前治疗策略的局限,讨论减轻毒性的工作,并概述未来研究方向。近期发现:靶向CD19的CAR-T细胞疗法(CD19-CAR)对复发/难治性(r/r)B细胞血液系统恶性肿瘤患者疗效显著。然而,出现了多项挑战,尤其是危及生命的不良事件,如细胞因子释放综合征和免疫效应细胞相关神经毒性综合征。尽管存在这些挑战,包括两项随机研究在内的近期CD19-CAR试验,既显示出令人瞩目的早期结果,也显示出持久应答。结合不断涌现的真实世界经验数据,CAR-T细胞疗效较高,推动研究扩展至其他B细胞抗原靶点〔如CD20、CD22和CD269(BCMA)〕以及其他血液系统恶性肿瘤靶点,并拓展至实体瘤和中枢神经系统(CNS)肿瘤。总结:鉴于CD19-CAR带来的获益,亟需确定它在个体患者治疗过程及更广义治疗范式中的适当位置。本文讨论探究这一问题的最新试验和领域未来方向。
PURPOSE OF REVIEW: The purpose of this review is to summarize the status and utilization of chimeric antigen receptor T-cell (CAR-T) therapy based on the most recent clinical trials in patients with leukemia and lymphoma. Additionally, this review will highlight limitations in current strategies, discuss efforts in toxicity mitigation, and outline future directions for investigation. RECENT FINDINGS: CD19 targeted CAR-T-cell therapy (CD19-CAR) is highly effective in patients with relapsed/refractory (r/r) B-cell hematologic malignancies. However, multiple challenges have arisen, particularly life-threatening adverse events, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Despite these challenges, recent CD19-CAR trials, including two randomized studies, have demonstrated both impressive initial results along with durable responses. Combined with results emerging from 'real-world' experience, the efficacy of CAR-T-cells is high, propelling CAR-T-cells studies targeting alternate B-cell antigens [e.g. CD20, CD22 and CD269 (BCMA)] and other targets for hematologic malignancies, along with solid and CNS tumors. SUMMARY: Given the benefit for CD19-CAR, determining the appropriate place in utilization for both an individual patient's treatment course and more broadly in the generalized treatment paradigm is critically needed. We discuss the most recent trials exploring this topic and future directions in the field.
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