| First Author | Canale FP | Year | 2021 |
| Journal | Nature | Volume | 598 |
| Issue | 7882 | Pages | 662-666 |
| PubMed ID | 34616044 | Mgi Jnum | J:325904 |
| Mgi Id | MGI:7287813 | Doi | 10.1038/s41586-021-04003-2 |
| Citation | Canale FP, et al. (2021) Metabolic modulation of tumours with engineered bacteria for immunotherapy. Nature 598(7882):662-666 |
| abstractText | The availability of L-arginine in tumours is a key determinant of an efficient anti-tumour T cell response(1-4). Consequently, increases of typically low L-arginine concentrations within the tumour may greatly potentiate the anti-tumour responses of immune checkpoint inhibitors, such as programmed death-ligand 1 (PD-L1)-blocking antibodies(5). However, currently no means are available to locally increase intratumoural L-arginine levels. Here we used a synthetic biology approach to develop an engineered probiotic Escherichia coli Nissle 1917 strain that colonizes tumours and continuously converts ammonia, a metabolic waste product that accumulates in tumours(6), to L-arginine. Colonization of tumours with these bacteria increased intratumoural L-arginine concentrations, increased the number of tumour-infiltrating T cells and had marked synergistic effects with PD-L1 blocking antibodies in the clearance of tumours. The anti-tumour effect of these bacteria was mediated by L-arginine and was dependent on T cells. These results show that engineered microbial therapies enable metabolic modulation of the tumour microenvironment leading to enhanced efficacy of immunotherapies. |
