具有Ab-TCR和共刺激受体的双受体T细胞平台实现了针对AML的特异性和功效
Tao Dao1, Guangyan Xiong2, Sung Soo Mun1
1Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY.
Blood
|December 4, 2023
概括
一种新型的双向化学抗原受体T细胞 (CAR T) 疗法,AbTCR-CSR,通过向WT1和CD33抗原,增强特异性和降低毒性,对急性髓性白血病 (AML) 显示出有前途.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 生物技术是生物技术.
背景情况:
- 化学抗原受体T细胞 (CAR T) 治疗在B细胞恶性瘤中取得了成功.
- 由于缺乏瘤特异性抗原和潜在的毒性,治疗固体瘤和其他血液癌症 (如急性髓性白血病 (AML)) 仍然存在挑战.
研究的目的:
- 开发一个双重向的CAR T细胞战略 (AbTCR-CSR) 针对AML.
- 设计针对威尔姆斯瘤1蛋白 (WT1) 和CD33抗原的T细胞,这些抗原在AML细胞上高度表达.
主要方法:
- 设计了一种新的T细胞平台,结合了向WT1的抗体-T细胞受体 (AbTCR) 和向CD33.3的仿真共刺激信号受体 (CSR).
- 使用TCR模仿单克隆抗体 (ESK2) 对抗WT1 RMF表位/HLA-A2复合体和单链可变片段对抗CD33.3.
主要成果:
- 改造的AbTCR-CSRT细胞对表达WT1和CD33.3的AML细胞表现出特定的细胞毒性.
- 这种方法节省了健康的造血细胞,包括正常的CD33+骨髓单细胞,表明减少了瘤外毒性.
结论:
- AbTCR-CSR平台代表了一种潜在的战略,用于改善AML采用T细胞治疗的特异性和降低毒性.
- 这种双重准的方法可以提高急性髓性白血病患者的临床结果.
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