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在放射治疗后长期缓解的单独口服CD30+/CD4+CAR+T细胞淋巴瘤

Evandro Bezerra¹, Ludmila Lupu², Marcos de Lima¹

¹The Ohio State University James Comprehensive Cancer Center, Columbus, OH 43210, USA.

Molecular therapy : the journal of the American Society of Gene Therapy

|September 4, 2025

概括

在化学抗原受体 (CAR) T 细胞治疗后的22个月内出现了一种罕见的T 细胞淋巴瘤 (TCL). 与治疗无关的遗传变化

科学领域:

癌症学
免疫疗法
遗传学

背景情况:

像tisagenlecleucel (tisa-cel) 一样, 化学抗原受体 (CAR) T细胞疗法是某些癌症的革命性治疗方法.
虽然有效,但了解长期副作用和潜在的二次恶性瘤对于患者的安全至关重要.
T细胞淋巴瘤 (TCL) 是一种罕见但严重的并发症,可能发生在CAR T细胞治疗后.

研究的目的:

在抗CD19CART细胞治疗后发生的CD30+/CD4+T细胞淋巴瘤 (TCL) 的单一病例.
在这种特定的CAR阳性TCL病例中调查淋巴发育的遗传基础.
强调在CAR T细胞治疗后对二次恶性瘤进行警的长期监测的重要性.

主要方法:

在CAR T细胞治疗后出现TCL的患者的临床病例介绍.
对TCL的分子分析,包括lentiviral整合部位分析.
对基因突变 (TET2),拷贝数变异 (NTRK1) 和基因融合 (ANKHD1-EIF4EBP3) 等遗传变化的评估.

主要成果:

在接受tisa- cel治疗22个月后,一名患者出现了CD30+/ CD4+T细胞淋巴瘤 (TCL).
在ANKHD1-EIF4EBP3,TET2功能丧失突变和NTRK1拷贝数增加中表现出lentiviral整合.
这些遗传变化表明淋巴发育独立于CAR治疗的插入性突变.

结论:

这是一个罕见的CAR- T细胞治疗后的CAR阳性TCL病例.
与CAR T细胞集成无关的基因变异似乎在这种二次恶性瘤的发展中起作用.
患者通过放射治疗得到缓解, 这表明需要继续研究治疗这种罕见的并发症.

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