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:CAR-T cell therapy in T-Cell lymphoblastic leukemia/lymphoma: where do we stand now?
CAR-T 治疗在复发/难治性 T-LL/L 中取得高缓解率,并可能作为异基因移植的桥接。
引言:复发或难治性(r/r)T细胞急性淋巴细胞白血病/淋巴瘤(T-LL/L)的CAR-T治疗面临挑战,现有临床研究多为小规模、分散队列,且常与临床前研究一并综述。本综述仅关注临床研究,评估CAR构型、安全性和疗效。方法:系统检索数据库、临床试验注册平台及会议摘要(2014年6月至2024年6月)。排除临床前研究及缺乏临床细节的研究。分析患者人口学特征、CAR-T特征、应答率、生存和不良事件。结果:共发现11种靶向CD7的CAR-T构型和2种靶向CD5的构型。完全缓解(CR/CRi)率为55%–100%,多数研究超过80%。复发率为7%–66%,且常发生于髓外部位。细胞因子释放综合征和神经毒性通常可控。移植物抗宿主病(GVHD)发生率不一(0–60%),主要见于异体CAR-T受者。治疗相关死亡中,感染占6%–38%。结论:CAR-T治疗r/r T-LL/L可获得较高应答率,并可作为异基因移植的桥接治疗。但随访时间较短,缓解持续时间仍令人担忧;GVHD、免疫恢复和感染控制等挑战仍然存在。未来试验需采用标准化报告,以优化疗效和安全性。注册:PROSPERO(CRD420251024662)。
INTRODUCTION: CAR-T therapies for relapsed or refractory (r/r) T-cell lymphoblastic leukemia/lymphoma (T-LL/L) faces challenges, with most clinical studies conducted in small, dispersed cohorts and often reviewed alongside preclinical studies. This review focuses exclusively on clinical studies, evaluating CAR constructs, safety and efficacy. METHODS: A systematic review was conducted of databases, clinical trial registries, and abstracts from conferences (June 2014 to June 2024). Preclinical studies and studies lacking clinical details were excluded. Data on patient demographics, CAR-T characteristics, response rates, survival, and adverse events were analyzed. RESULTS: Eleven CAR-T constructs targeting CD7 and two targeting CD5 were identified. Complete remission (CR/CRi) rates ranged from 55% to 100%, exceeding 80% in most studies. Relapse, often in extramedullary sites, ranged from 7% to 66%. Cytokine release syndrome and neurotoxicity were generally manageable. GVHD incidence varied (none to 60%), primarily in allogeneic CAR-T recipients. Infections contributed to 6-38% of treatment-related mortality. CONCLUSIONS: CAR-T therapy achieves high response rates in r/r T-LL/L and may serve as a bridge to allogeneic transplantation. However, the short follow-up and the duration of responses remain concerns, and challenges endure, including GVHD, immune recovery and infection control. Standardized reporting is crucial to optimize therapy outcomes and safety in future trials. REGISTRATION: PROSPERO (CRD420251024662).
MEMBER ACCOUNT
登录成功会直接打开下一页。