期刊
BLOOD
卷 136, 期 10, 页码 1155-1160出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2019004500
关键词
-
类别
资金
- Cancer Research UK
- Treating Children with Cancer
- Amber Phillpott Trust
- Birmingham Children's Hospital
- Phenome Centre Birmingham [MR/M009157/1]
- MRC [MC_PC_16047, MC_PC_18051] Funding Source: UKRI
Hematological and solid cancers catabolize the semiessential amino acid arginine to drive cell proliferation. However, the resulting low arginine microenvironment also impairs chimeric antigen receptor T cells (CAR-T) cell proliferation, limiting their efficacy in clinical trials against hematological and solid malignancies. T cells are susceptible to the low arginine microenvironment because of the low expression of the arginine resynthesis enzymes argininosuccinate synthase (ASS) and ornithine transcarbamylase (OTC). We demonstrate that T cells can be reengineered to express functional ASS or OTC enzymes, in concert with different chimeric antigen receptors. Enzyme modifications increase CAR-T cell proliferation, with no loss of CAR cytotoxicity or increased exhaustion. In vivo, enzyme-modified CAR-T cells lead to enhanced clearance of leukemia or solid tumor burden, providing the first metabolic modification to enhance CAR-T cell therapies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据