Co-Expression of miR155 or LSD1 shRNA Increases the Anti-Tumor Functions of CD19 CAR-T Cells

Chimeric antigen receptor (CAR) T cells targeting CD19 antigen have produced remarkable clinical outcomes for cancer patients. However, identifying measures to enhance effector function remains one of the most challenging issues in CD19-targeted immunotherapy. Here, we report a novel approach in whi...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in immunology 2022-01, Vol.12, p.811364-811364
Main Authors: Zhang, Jing, Zhu, Jingjing, Zheng, Genhui, Wang, Qianyu, Li, Xiaorui, Feng, Yaru, Shang, Fengqin, He, Siqi, Jiang, Qiyao, Shi, Bingjie, Wang, Dong, Cao, Zhiwei, Wang, Jianxun
Format: Article
Language:English
Subjects:
Animals
Antigens, CD19 - immunology
CAR-T cells
CD19
Histone Demethylases - immunology
Humans
Immunology
Immunotherapy, Adoptive - methods
LSD1 shRNA
Mice
MicroRNAs - immunology
miR155
Neoplasms, Experimental - immunology
Receptors, Chimeric Antigen - immunology
retroviral vector
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Chimeric antigen receptor (CAR) T cells targeting CD19 antigen have produced remarkable clinical outcomes for cancer patients. However, identifying measures to enhance effector function remains one of the most challenging issues in CD19-targeted immunotherapy. Here, we report a novel approach in which a microRNA (miRNA) or short-hairpin RNA (shRNA) cassette was integrated into CAR-expressing retroviral vectors. Using this system, we generated anti-CD19 CAR-T cells co-expressing miR155 or LSD1 shRNA and found that anti-CD19 CAR-T cells with miR155 upregulation or LSD1 downregulation exhibited increased anti-tumor functions and . Transcriptional profiling analysis by RNA sequencing revealed the targets of miR155 and LSD1 in anti-CD19 CAR-T cells. Our experiments indicated that introduction of miRNA or shRNA expression into anti-CD19 CAR T-cells might be an effective strategy to improve the anti-tumor effects of CAR-T cell therapy.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.811364