针对GD2+脑髓母细胞瘤的GD2+患者的CAR T细胞疗法
Roselia Ciccone1, Concetta Quintarelli1,2, Antonio Camera1
1Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
概括
化学抗原受体 (CAR) 针对GD2的T细胞疗法显示出治疗脑膜母细胞瘤 (MB) 的前景,这是一种常见的儿童脑癌. 这种方法可能会提供比目前的疗法更有效的治疗,副作用更少.
科学领域:
- 儿科瘤学 儿科瘤学
- 免疫治疗是一种免疫疗法.
- 神经瘤学神经瘤学
背景情况:
- 骨髓母细胞瘤 (MB) 是最常见的儿科恶性脑瘤,大约30%的患者预后不佳.
- 目前的标准治疗 (手术,放射,化疗) 可以导致显著的长期认知,神经和内分泌副作用.
研究的目的:
- 调查针对disialoganglioside GD2的化学抗原受体 (CAR) T细胞的潜力,作为更有效的MB治疗方法.
- 评估CAR T细胞疗法是否可以减少与传统MB治疗相关的长期副作用.
主要方法:
- 在使用流细胞计的儿科MB瘤活检中分析了GD2表达.
- GD2表达是由EZH2抑制剂tazemetostat调节的.
- CAR.GD2 T细胞在体外和体内进行了开发和测试,并为安全性添加了自杀基因.
主要成果:
- 在82.68%的MB瘤中表达了GD2,在SHH和G3-G4亚型中水平更高.
- CAR.GD2 T细胞在体外证明了对GD2+ MB细胞的细胞毒性.
- 塔泽梅托斯塔特前期治疗增强了GD2表达,增加了MB细胞对CAR.GD2T细胞的敏感性.
- 在体内研究表明,CAR.GD2 T细胞控制了瘤生长,并在MB小鼠模型中延长了生存时间.
- 自杀基因系统在体内有效地消除了CAR.GD2 T细胞.
结论:
- CAR.GD2 T细胞疗法显示出治疗脑髓母细胞瘤的潜在疗效.
- 一个I/II期临床试验 (NCT05298995) 正在进行中,以评估CAR.GD2治疗在高危MB患者中的安全性和有效性.
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