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 Efficacy and Safety of CD7-Targeted CAR T Cell Therapy for T-cell Malignancies: A Systematic Review and Meta-analysis.
CD7是一个活跃且安全的靶点,在治疗复发和/或难治性(r/r)T细胞恶性肿瘤方面显示出有希望的结果。
尽管与B细胞恶性肿瘤相比,T细胞恶性肿瘤的发病率相对较低,但其恶性程度高,患者预后通常较差。采用CD7靶向嵌合抗原受体(CAR)T细胞疗法作为治疗恶性T细胞的新型免疫疗法面临诸多挑战,且仍处于早期阶段。为评估这一可能性,我们旨在系统性地回顾并荟萃分析相关临床试验。
2023年10月9日,系统检索了PubMed、Scopus、Embase和Web of Science在线数据库中的相关研究。完成两步标题/摘要和全文筛选流程后,纳入符合条件的研究。
我们观察到汇总的总体缓解率(ORR)为100%。部分缓解(PR)、严格和/或完全缓解(sCR/CR)以及复发率分别为6%、85%和18%。此外,汇总的微小残留病(MRD)阴性率为85%。最常见的3级不良事件与血液学毒性相关,包括中性粒细胞减少(100%)、血小板减少(79%)和贫血(57%)。细胞因子释放综合征(CRS)也是常见的并发症,发生率为100%;然而,81%的CRS事件为低级别。未报告3级GVHD,免疫效应细胞相关神经毒性综合征(ICANS 3级)罕见(4%)。
OBJECTIVES: Although T-cell malignancies are relatively less prevalent compared to B-cell malignancies, they are highly malignant, and patients usually have poor prognoses. Employing CD7-targeted chimeric antigen receptor (CAR) T cell therapy as a novel immunotherapy to treat malignant T cells faces numerous challenges and is in its early phase. To evaluate this possibility, we aimed to review and meta-analyze the related clinical trials systematically. METHODS: On October 9, 2023, the online databases of PubMed, Scopus, Embase, and Web of Science were systematically searched for pertinent studies. After completing a two-step title/abstract and full-text screening process, the eligible studies were included. RESULTS: We observed a pooled overall response rate (ORR) of 100%. Partial response (PR), stringent and/or complete response (sCR/CR), and relapse rate were 6%, 85%, and 18%, respectively. Additionally, the pooled rate of minimal residual disease (MRD) negativity was 85%. The most common grade 3 adverse events were related to hematological toxicities, including neutropenia (100%), thrombocytopenia (79%), and anemia (57%). Cytokine release syndrome (CRS) was also a frequent complication with a 100% rate; however, 81% of CRS events were low grades. No grade 3 GVHD was reported, and the immune effector cell-associated neurotoxicity syndrome (ICANS grade 3) was rare (4%). CONCLUSION: CD7 is an active and safe target that shows promising results in the treatment of relapsed and/or refractory (r/r) T-cell malignancies.
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