针对CD19和CD37的双CAR-T细胞在向抗原损失B细胞瘤模型中有效
Kanae Imai1, Yuki Takeuchi1, Seitaro Terakura1
1Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Molecular cancer therapeutics
|October 13, 2023
概括
识别CD19和CD37抗原的双向CAR-T细胞对异质B细胞瘤的疗效提高. 这些仿真抗原受体T细胞为复发性/耐药性B细胞恶性瘤提供了一个有前途的策略.
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:
- 由于抗原丢失而导致的免疫逃脱在CAR-T细胞治疗中是一个挑战.
- 向多个抗原可能可以克服这一局限性,并提高治疗效率.
研究的目的:
- 开发和评估针对CD19和CD37抗原的双向化学抗原受体T (CAR-T) 细胞.
- 为了评估这些双 CAR-T 细胞的抗瘤作用,试验室和活体模型.
主要方法:
- 通过共传导和同时基因转移使用lentiviral载体生成CD19/CD37双CAR-T细胞.
- 评估了CAR-T细胞增殖,细胞因子生产,细胞内信号传递和对B细胞瘤模型的细胞毒性.
- 在使用抗原异质拉吉细胞的异种移植小鼠模型中评估了疗效.
主要成果:
- CD19/CD37双卡特-T细胞在刺激时表现出足够的增殖和细胞因子的产生.
- 双 CAR-T 细胞的信号传递和细胞毒性与单个 CAR-T 细胞对同质瘤的信号传递和细胞毒性相似.
- 对抗原异质瘤的双 CAR-T 细胞观察到明显优异的瘤溶解.
- 在异种移植小鼠模型中证明了对抗原异质拉吉细胞的有效抑制.
结论:
- CD19/CD37双CAR-T细胞在体外和体内对抗原损失B细胞瘤模型有效.
- 这种双重向的方法代表了复发性/耐药性B细胞恶性瘤的有前途的治疗策略.
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