透到CAR修饰的髓淋巴细胞有效向具有非常低抗原密度的恶性血细胞
Nicolas Camviel1, Davide Gambarotto2, Violaine Andre1
1Department of oncology UNIL-CHUV, University Hospital Lausanne (CHUV) and University of Lausanne (UNIL), 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research Lausanne, 1011 Lausanne, Switzerland; Swiss Cancer Center Léman, 1011 Lausanne, Switzerland; AGORA Cancer Research Center, 1011 Lausanne, Switzerland.
概括
针对BCMA和TACI的化学抗原受体 (CAR) T细胞对多发性骨髓瘤 (MM) 有希望. 双重向的CAR-T细胞有效地杀死癌细胞,即使抗原水平低,这表明TACI是可行的目标.
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:
- B细胞成熟抗原 (BCMA) 是多发性骨髓瘤 (MM) 免疫疗法的关键标.
- 频繁复发需要除BCMA之外的替代治疗点.
研究的目的:
- 研究一种双特异化基因抗原受体 (CAR) T细胞治疗的有效性,该疗法针对MM的BCMA和跨膜激活剂和CAML相互作用体 (TACI) 进行向.
- 评估来自患者骨髓透淋巴细胞 (MILs) 的CAR T细胞杀死MM细胞.
主要方法:
- 开发一个双特异性的CAR,承认BCMA和TACI.
- 在患者衍生的MILs中表达CAR的表达.
- 使用流细胞计和直接随机光学重建显微镜 (dSTORM) 评估MM细胞杀死.
主要成果:
- 汽车T细胞有效地杀死恶性血细胞 (PCs),尽管流细胞计通过低或不可检测的抗原水平.
- 与流动细胞计量相比,dSTORM显示显著低估了BCMA和TACI表达水平.
- 在非常低的抗原密度下,CAR T细胞表现出多功能杀伤能力.
结论:
- 跨膜激活剂和CAML相互作用剂 (TACI) 是MM治疗的一个有前途的目标.
- 超分辨率显微镜 (dSTORM) 对于评估CAR T细胞疗法的抗原密度值是有价值的.
- 双重向的CAR-T细胞提供了对抗多发性骨髓瘤的有效策略.
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