相关实验视频
Updated: Sep 12, 2025

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Production of Human CRISPR-Engineered CAR-T Cells
Published on: March 15, 2021
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[下一代CAR基因修饰细胞疗法:克服耐药性和探索新型应用]
1Division of Hematology, Mayo Clinic.
概括
化学抗原受体 (CAR) T细胞疗法对多发性骨髓瘤具有前景,但面临瘤微环境挑战. 这项研究开发了双特异性的CAR T细胞和CAR工程介质干细胞,以克服这些局限性并减少移植对宿主疾病.
科学领域:
- 免疫治疗是一种免疫疗法.
- 细胞疗法细胞疗法
- 癌症研究 癌症研究
背景情况:
- 化学抗原受体 (CAR) T细胞疗法对多发性骨髓瘤 (MM) 是有前途的,但由于瘤微环境 (TME) 导致的耐用性面临挑战.
- 在TME内的癌症相关纤维细胞 (CAF) 促进免疫抑制和CAR T细胞功能障碍.
研究的目的:
- 调查CAFs如何损害MM中的BCMA CAR T细胞功能.
- 开发针对MM细胞和CAF的双特异性CAR-T细胞.
- 为减轻移植对宿主疾病 (GvHD) 进行CAR介质干细胞 (MSC) 的工程.
主要方法:
- 解析的CAF介导抑制途径包括TGF-β,PD-L1,IL-10和FAS/FASL.
- 开发了针对MM和CAF的双特异CAR-T细胞 (BCMA-FAP和BCMA-CS1).
- 设计了针对E-cadherin的CAR MSCs (Ecad CAR-MSCs) 来管理GvHD.
主要成果:
- 发现CAFs通过特定的分子通路促进CAR T细胞疲劳.
- BCMA-FAP和BCMA-CS1 CAR T细胞对MM细胞和CAFs表现出增强的细胞毒性,克服了TME诱导的抑制.
- Ecad CAR-MSCs通过向肠表皮和调节T细胞响应通过IL-10和加勒-9来有效地降低GvHD,促进Treg诱导.
结论:
- 针对CAF的双特异性CAR T细胞增强了MM免疫治疗的疗效.
- 埃卡德CAR-MSCs代表了治疗GvHD的新战略.
- 这些工程细胞疗法显示出临床翻译的潜力,以改善细胞疗法结果.
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