| 项目编号 | PRJCA011606 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 项目标题 | Knocking out BATF improves CAR-T cell efficacy by resisting exhaustion and forming central memory cells | ||||||||||
| 涉及领域 | Medical | ||||||||||
| 先导项目 |
eGPS: evolutionary Genotype-Phenotype Systems biology Plateau Adaptability Analysis of adaptive traits in the Qinghai Tibet Plateau |
||||||||||
| 数据类型 | Exome | ||||||||||
| 物种名称 |
Mus musculus
Homo sapiens |
||||||||||
| 描述信息 | Chimeric antigen receptor modified T (CAR-T) cell therapy has limited efficacy against solid tumor, one major challenge is T cell exhaustion. To address this challenge, we performed a candidate gene screen using a hypofunction CAR-T cell model, and found that knocking out BATF improved the performance of CAR-T cells. In different types of CAR-T cells and mouse OT-1 cells, knocking out BATF endows T cells with improved resistance to exhaustion and better tumor eradication efficacy. We find that BATF binds to and up-regulates a subset of exhaustion genes in human CAR-T cells. Furthermore, BATF regulates the expression of genes involved in the development of effector and memory cells, and knocking out BATF shifts the population towards more central memory subset. Therefore, we conclude that BATF is a key factor limiting CAR-T cell function, and its depletion improves CAR-T cells efficacy against solid tumor. | ||||||||||
| 样品范围 | CAR-T cells | ||||||||||
| 发布日期 | 2022-09-01 | ||||||||||
| 出版信息 |
|
||||||||||
| 项目资金来源 |
|
||||||||||
| 提交者 | Xingying Zhang (zhangxingying@ioz.ac.cn) | ||||||||||
| 提交单位 | Institute of Zoology, Chinese Academy of Sciences | ||||||||||
| 提交日期 | 2022-09-01 |