LRRC15-CAR T细胞用于治疗骨髓瘤
Carla O'Reilly1, Shraddha Tuladhar1, Phuong Nguyen1
1St. Jude Children's Research Hospital Memphis, TN United States.
概括
化学抗原受体 (CAR) T细胞治疗向含有氨酸丰富的重复15 (LRRC15) 显示出对骨髓瘤的承诺. 在临床前模型中,LRRC15-CAR T细胞表现出显著的抗瘤活性和有利的安全性.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 细胞疗法细胞疗法
背景情况:
- 骨肉瘤对化学抗原受体 (CAR) T 细胞疗法提出了挑战,因为需要新的标.
- 含有氨酸丰富的重复15 (LRRC15) 已成为治疗骨髓瘤的有前途的向抗原.
研究的目的:
- 开发和评估LRRC15特异性CAR T细胞用于骨髓瘤的临床前疗效和安全性.
- 评估LRRC15在正常组织和骨髓瘤中的表达,以验证其作为治疗点.
主要方法:
- 在正常组织和儿科固体瘤中通过基因表达和免疫组织化学分析LRRC15的表达.
- LRRC15-CAR T细胞在异种移植和同源性骨髓癌模型中被设计并测试了特异性,体外细胞毒性和体内抗瘤活性.
- 对静脉注射的LRRC15-CAR T细胞进行了全面的安全性和毒性分析.
主要成果:
- LRRC15在正常组织中表达有限,但在骨髓瘤中表达高,在基因和蛋白质层面.
- 在实验室中,LRRC15-CAR T细胞对LRRC15-阳性标表现出特定的细胞毒性.
- 在体内研究表明,在骨髓瘤模型中显著的抗瘤作用和改善的生存率,具有积极的安全性.
结论:
- LRRC15-CAR T细胞有效地向并减少骨髓瘤的生长,同时保持良好的安全性.
- 这些发现支持LRRC15-CAR T细胞治疗骨髓瘤和潜在的其他LRRC15阳性固体瘤的临床转化.
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