CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:INSPIRED Symposium Part 2: Prevention and Management of Relapse Following Chimeric Antigen Receptor T Cell Therapy for B Cell Acute Lymphoblastic Leukemia.
INSPIRED Symposium Part 2: Prevention and Management of Relapse Following Chimeric Antigen Receptor T Cell Therapy for B Cell Acute Lymphoblastic Leukemia.
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尽管靶向 CD19 的嵌合抗原受体(CAR)T 细胞疗法(CAR-T)可诱导并维持复发/难治性 B 急性淋巴细胞白血病(B-ALL)患者缓解,复发率仍高得无法接受;约 50% 的儿童和年轻成人在输注后第一年内复发。正在出现的延长缓解持续时间策略包括利用预后生物标志物识别复发高风险患者,或采取措施增强 CAR-T 细胞功能性持久性。然而,抗原丢失/下调或谱系转换是复发的主要机制,仅优化单一抗原靶向并不足够。本文重点讨论复发预防策略,包括输注后监测和正在探索的 CAR-T 后治疗方法(如联合靶向多个抗原、预防性造血细胞移植),综述 CAR-T 后复发预防和管理的最新进展。我们总结该领域的发展,并指出文献空白,为未来优化儿童和年轻成人 B-ALL 患者 CAR-T 后复发预防与管理的研究提供方向。
Although CD19-directed chimeric antigen receptor (CAR) T cell therapy (CAR-T) for relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) has been transformative in inducing and sustaining remission, relapse rates remain unacceptably high, with approximately 50% of children and young adults experiencing relapse within the first year postinfusion.
Emerging strategies to extend the durability of remission involve the use of prognostic biomarkers to identify those at high risk of relapse or incorporate strategies aimed to enhancing functional CAR T cell persistence. Nonetheless, with antigen loss/down-regulation or evolution to lineage switch as major mechanisms of relapse, optimizing single antigen targeting alone is insufficient.
Here, with a focus on relapse prevention strategies, including postinfusion surveillance and treatment approaches being explored to optimize post-CAR-T management (eg, combinatorial antigen targeting strategies, preemptive hematopoietic cell transplantation), we review the current state of the art in the prevention and management of post CAR-T relapse.
We highlight the advancements in the field and identify gaps in the literature to guide future research in optimizing the prevention and management of post-CAR-T relapse in children and young adults with B-ALL.
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