在制造过程中GD2TRAC-CAR T细胞的代谢原始化促进了记忆表型,同时增强了持久性
Dan Cappabianca1,2, Dan Pham2,3, Matthew H Forsberg4
1Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
概括
在CAR T细胞制造过程中的代谢原始化优化了细胞表型. 这一过程丰富了记忆T细胞并提高了持久性,在体内潜在地增强了抗瘤反应.
科学领域:
- 细胞免疫疗法细胞免疫疗法
- 生物制造 生物制造 生物制造
- 癌症研究 癌症研究
背景情况:
- 制造仿真抗原受体 (CAR) T细胞疗法是复杂的.
- 中等成分对T细胞表型的影响尚未完全理解.
- 克里斯普尔-Cas9可实现精确的CAR插入和基因破坏 (TRAC),用于增强的T细胞群.
研究的目的:
- 调查代谢原始化 (MP) 对 TRAC-CAR T 细胞制造的影响.
- 优化CAR T细胞表型,以提高对固体瘤的疗效.
主要方法:
- 使用两阶段的中介组成策略 (代谢原始化) 生成抗GD2 TRAC-CAR T细胞.
- 使用光谱流细胞计,代谢测试,细胞因子分析和体外/体内活性测试评估的T细胞产品.
- 对人类GD2+异种移植神经母细胞瘤模型的评估有效性.
主要成果:
- MP TRAC-CAR T细胞表现出减少的糖解和减少某些细胞因子 (IFN-γ,IL-2,IL-10,IL-1β,IL-17,TGF-β) 的产生.
- MP增强了中央记忆的CAR T细胞群体 (更高的CR7 / CD62L表达,增加了NAD (P) H活性).
- 在体内,MP CAR T细胞表现出对神经母细胞瘤异种移植的改善持久性和功效.
结论:
- 在CAR T细胞生物制造过程中的代谢原始化将糖分分解降到最低,并丰富出活体记忆表型.
- 通过MP优化的T细胞产品显示出在体内改善对固体瘤的反应的潜力.
- 中等成分是优化CAR T细胞治疗制造的关键因素.
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