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感染温度会影响慢病毒技术制备的嵌合抗原受体 T 细胞的表型和功能。

Infection Temperature Affects the Phenotype and Function of Chimeric Antigen Receptor T Cells Produced Lentiviral Technology.

机构信息

Nankai University School of Medicine, Tianjin, China.

Department of Hematology, Tianjin First Central Hospital, Tianjin, China.

出版信息

Front Immunol. 2021 Apr 19;12:638907. doi: 10.3389/fimmu.2021.638907. eCollection 2021.

DOI:10.3389/fimmu.2021.638907
PMID:33953713
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8089475/
Abstract

Chimeric antigen receptor (CAR)-T cell therapy has become an important method for the treatment of hematological tumors. Lentiviruses are commonly used gene transfer vectors for preparing CAR-T cells, and the conditions for preparing CAR-T cells vary greatly. This study reported for the first time the influence of differences in infection temperature on the phenotype and function of produced CAR-T cells. Our results show that infection at 4 degrees produces the highest CAR-positive rate of T cells, infection at 37 degrees produces the fastest proliferation in CAR-T cells, and infection at 32 degrees produces CAR-T cells with the greatest proportion of naive cells and the lowest expression of immune checkpoints. Therefore, infection at 32 degrees is recommended to prepare CAR-T cells. CAR-T cells derived from infection at 32 degrees seem to have a balance between function and phenotype. Importantly, they have increased oncolytic ability. This research will help optimize the generation of CAR-T cells and improve the quality of CAR-T cell products.

摘要

嵌合抗原受体 (CAR)-T 细胞疗法已成为治疗血液系统肿瘤的重要方法。慢病毒是常用于制备 CAR-T 细胞的基因转移载体，制备 CAR-T 细胞的条件差异很大。本研究首次报道了感染温度差异对产生的 CAR-T 细胞表型和功能的影响。我们的结果表明，4℃感染可产生最高的 CAR 阳性 T 细胞率，37℃感染可使 CAR-T 细胞增殖最快，32℃感染可产生具有最大比例幼稚细胞和最低免疫检查点表达的 CAR-T 细胞。因此，建议在 32℃下进行感染来制备 CAR-T 细胞。32℃感染衍生的 CAR-T 细胞在功能和表型之间似乎达到了平衡。重要的是，它们具有增强的溶瘤能力。这项研究将有助于优化 CAR-T 细胞的生成，提高 CAR-T 细胞产品的质量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/6b9a245f7e20/fimmu-12-638907-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/cfc087cc736f/fimmu-12-638907-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/0c09462ac2a9/fimmu-12-638907-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/53c38f8182b8/fimmu-12-638907-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/f315ba692553/fimmu-12-638907-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/6b9a245f7e20/fimmu-12-638907-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/cfc087cc736f/fimmu-12-638907-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/0c09462ac2a9/fimmu-12-638907-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/53c38f8182b8/fimmu-12-638907-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/f315ba692553/fimmu-12-638907-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dce2/8089475/6b9a245f7e20/fimmu-12-638907-g005.jpg

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