基于TCR模仿纳米体的CAR-T细胞向HPV16 E6,表现出对宫癌的抗瘤活性
Zhijian Duan1, Dan Li2, Nan Li2
1Antibody Engineering Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Molecular therapy. Oncology
|November 11, 2024
概括
针对人类乳头瘤病毒 (HPV) 基蛋白的新型纳米体显示出治疗HPV相关癌症的前景. 基于F5纳米体的CAR-T细胞有效地杀死癌细胞,并抑制小鼠的瘤生长.
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:
- 人类乳头瘤病毒 (HPV) 型蛋白E6和E7是HPV相关癌症的关键标.
- 化学抗原受体 (CAR) T细胞疗法为癌症治疗提供了一个潜在的策略.
研究的目的:
- 为了评估针对HPV E6-HLA复合体的CAR格式的新型T细胞受体模拟器 (TCRm) 纳米体.
- 评估基于F5纳米体的CAR-T细胞对HPV相关癌症的疗效.
主要方法:
- 通过菌体显示,将驼纳米体 (F5和G9) 隔离,以准E6-HLA-A*02:01复合体.
- 对纳米体结合目标细胞和CAR-T细胞介导的杀死in vitro的评估.
- 对CAR-T细胞信号通路 (NFAT和NF-κB) 的评估.
- 在实体研究中,使用小鼠瘤异种移植来评估F5 CAR-T细胞的疗效.
主要成果:
- 与G9.9相比,纳米体F5在各种癌症细胞系上对HPV E6-HLA复合体具有优越的结合.
- F5 CAR-T细胞表现出特定的杀向癌细胞in vitro,通过激活NFAT和NF-κB信号.
- 在小鼠中,F5 CAR-T细胞显著抑制了HPV-16+宫癌异种移植的生长.
结论:
- 基于F5纳米体的CAR-T细胞有效地向和消除HPV-16+宫癌细胞.
- 这种方法为HPV-16+恶性瘤提供了一个有希望的替代治疗策略.
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