IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities

作者全名："Du, Li; Nai, Yaru; Shen, Meiying; Li, Tingting; Huang, Jingjing; Han, Xiaojian; Wang, Wang; Pang, Da; Jin, Aishun"

作者地址："[Du, Li; Nai, Yaru; Li, Tingting; Huang, Jingjing; Han, Xiaojian; Wang, Wang; Jin, Aishun] Chongqing Med Univ, Chongqing Key Lab Basic & Translat Res Tumor Immu, Chongqing, Peoples R China; [Shen, Meiying; Pang, Da] Harbin Med Univ, Canc Hosp, Dept Breast Surg, Harbin, Peoples R China"

通信作者："Jin, AS (corresponding author), Chongqing Med Univ, Chongqing Key Lab Basic & Translat Res Tumor Immu, Chongqing, Peoples R China.; Pang, D (corresponding author), Harbin Med Univ, Canc Hosp, Dept Breast Surg, Harbin, Peoples R China."

来源：FRONTIERS IN MOLECULAR BIOSCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000662915300001

JCR分区：Q2

影响因子：5

年份：2021

卷号：8

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：CAR-T; IL-21; transfection; IFN-gamma; cytotoxicity

摘要："Adoptive immunotherapy using CAR-T cells is a promising curative treatment strategy for hematological malignancies. Current manufacture of clinical-grade CAR-T cells based on lentiviral/retrovirus transfection of T cells followed by anti-CD3/CD28 activation supplemented with IL-2 has been associated with low transfection efficiency and usually based on the use of terminally differentiated effector T cells. Thus, improving the quality and the quantity of CAR-T cells are essential for optimizing the CAR-T cell preparation. In our study, we focus on the role of IL-21 in the gamma(c) cytokine conditions for CAR-T cell preparation. We found for the first time that the addition of IL-21 in the CAR-T preparation improved T cell transfection efficiency through the reduction of IFN-gamma expression 24-48 h after T cell activation. We also confirmed that IL-21 enhanced the enrichment and expansion of less differentiated CAR-T cells. Finally, we validated that IL-21 improved the CAR-T cell cytotoxicity, which was related to increased secretion of effector cytokines. Together, these findings can be used to optimize the CAR-T cell preparation."

基金机构：National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81572807]

基金资助正文："This research was funded by National Natural Science Foundation of China, Grant Number 81572807."