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:Challenges and advances in CAR-T cell therapy for B-ALL.
CAR-T 细胞疗法已彻底改变了复发/难治性B细胞急性淋巴细胞白血病(R/R B-ALL)等血液系统恶性肿瘤的治疗格局,目前全球已有多种CAR-T产品获批用于R/R B-ALL的治疗。
CAR-T 细胞疗法革新了复发/难治性 B 急性淋巴细胞白血病(R/R B-ALL)等血液系统恶性肿瘤的治疗格局,目前已有多种 CAR-T 产品在全球获批用于 R/R B-ALL。尽管初始应答率较高,仍面临重大挑战,包括抗原逃逸导致疾病复发、CAR-T 持续性有限;细胞因子释放综合征、免疫效应细胞相关神经毒性综合征、血液学毒性和感染等治疗相关不良事件;以及 CAR-T 可及性有限。本综述讨论 CAR-T 的局限及克服策略,重点关注 B-ALL,包括异体 CAR-T、双靶向 CAR-T,以及与新技术和药物联合的方案。文章还探讨 CAR-T 后巩固性异基因造血干细胞移植的作用,以及将 CAR-T 纳入 B-ALL 一线治疗的可能性。未来研究应致力于提高 CAR-T 疗效、降低毒性、改善可及性,并推动其在 B-ALL 更早治疗线中的应用。
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment landscape for hematological malignancies such as relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), with several CAR-T products now approved globally for R/R B-ALL. Despite high initial response rates, major challenges remain, including disease relapse due to antigen escape and the limited persistence of CAR-T cells; treatment-related adverse events such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, hematologic toxicity, and infections; and limited access to CAR-T therapy. In this review, we discuss the limitations of CAR-T and strategies to overcome them, specifically in the context of B-ALL, including the use of allogeneic CAR-T, dual-targeted CAR-T, and combination strategies with novel technologies and agents. Furthermore, we explored the role of consolidative allogeneic hematopoietic stem cell transplantation after CAR-T therapy and the potential of integrating CAR-T into the first-line treatment for B-ALL. Future research should aim to increase the efficacy of CAR-T, reduce their toxicity, improve their accessibility, and expand their use to earlier lines of therapy for B-ALL.
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