介素-27的构成表达减少了促炎性细胞因子的产生,而不会损害工程T细胞的效应器功能

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Arya Afsahi¹, Rebecca Burchett¹, Christopher L Baker¹

¹Centre for Discovery in Cancer Research, McMaster University, Hamilton, Ontario, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

|June 12, 2023

概括

工程T细胞表达Interleukin (IL) -27增强抗髓瘤免疫力,减少有害的炎症性细胞因子. 这种方法可以减轻与T细胞疗法相关的毒性.

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:

免疫调节性细胞因子可以重塑瘤微环境,以加强瘤根除.
干白素 (IL) -27是一种细胞因子,具有增强抗瘤免疫力和抗髓瘤活性的证明潜力.

研究的目的:

为了设计人类T细胞来表达单链 (sc)IL-27.
在针对骨髓瘤的B细胞成熟抗原 (BCMA) 向治疗的背景下,评估用于表达scIL-27的T细胞的抗瘤功能和细胞因子概况.

主要方法:

人类T细胞经过基因改造,共同表达一种复合单链 (sc) IL-27和一种针对髓瘤特异性抗原BCMA的仿制抗原受体 (CAR).
这些工程T细胞的抗瘤疗效和细胞因子生产通过体外和体内实验进行了评估.

主要成果:

使用scIL-27进行工程的T细胞表现出持续的抗瘤免疫力和对髓瘤细胞的细胞毒性.
在scIL-27-表达T细胞中观察到,促炎性细胞因子的分泌显著减少,包括花细胞-巨细胞殖民地刺激因子 (GM-CSF) 和瘤缩因子α (TNF-α).

结论:

同时表达scIL-27的工程T细胞保持强大的抗髓瘤活性.
减少了scIL-27表达T细胞的亲炎性细胞因子,这为缓解工程T细胞疗法中常见的与治疗相关的毒性提供了潜在的策略.

关键词:

在IL-27和IL-27之间.这是一辆卡车.癌症免疫疗法免疫疗法工程T细胞的工程T细胞.多发性骨髓瘤是多发性骨髓瘤的一种.

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