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T细胞激活剂对化学抗原受体T细胞表现型和功能表现出明显的下游影响

Sarah Underwood¹, Jianjian Jin¹, Lipei Shao¹

¹Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD.

|June 12, 2024

概括

不同的T细胞激活试剂显著影响着仿真抗原受体 (CAR) T细胞制造. 抗CD3/抗CD28刺激的输送方法会影响CAR T细胞扩张,功能和表型,从而影响临床产品的质量.

科学领域:

免疫学免疫学免疫学
生物技术是生物技术.
细胞疗法细胞疗法

背景情况:

T细胞激活对于化学抗原受体 (CAR) T细胞制造至关重要.
激活剂试剂触发T细胞受体 (TCR) 并提供共刺激,影响CAR T细胞培养属性.

研究的目的:

探索各种T细胞激活试剂及其对CAR T细胞属性的影响.
检查抗CD3/抗CD28的不同传递机制如何影响CAR T细胞激活,扩张,基因表达和功能.

主要方法:

测试了四种不同的激活剂:Dynabeads,TransAct,Cloudz和Microbubbles,所有这些都使用了抗CD3和抗CD28.
细胞被用编码双价CD19/CD22 CAR的晶状病毒载体转化.
细胞计数和流细胞计量监测培养物;功能测试评估了细胞杀死和细胞因子分泌.

主要成果:

克劳兹激活剂使CD4/CD8比率偏向CD8T细胞.
迪纳珠刺激产生了最高的天真T细胞子集,而Cloudz产生了最多的效应/效应记忆细胞.
克劳兹刺激的细胞表现出最高的目标细胞杀死和促炎性细胞因子分泌.

结论:

向T细胞呈现刺激性抗体的方法会影响CAR T细胞的激活和功能.
不同的T细胞激活试剂导致不同的CAR T细胞产品属性.
这些发现对于优化用于临床应用的CAR T细胞制造至关重要.

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