| First Author | Fultang L | Year | 2020 |
| Journal | Blood | Volume | 136 |
| Issue | 10 | Pages | 1155-1160 |
| PubMed ID | 32573723 | Mgi Jnum | J:304070 |
| Mgi Id | MGI:6508825 | Doi | 10.1182/blood.2019004500 |
| Citation | Fultang L, et al. (2020) Metabolic engineering against the arginine microenvironment enhances CAR-T cell proliferation and therapeutic activity. Blood 136(10):1155-1160 |
| abstractText | 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. |
