577 Engineered non-pathogenic synthetic biotic producing L-arginine synergize with PD-1-based cancer immunotherapy
| Autor: | Roger Geiger, Jose M. Lora, Jean-Philippe Theurillat, Michael J. James, Fernando P. Canale, Wenjie Jin, Camilla Basso, Ning Li, Anna Sokolovska, Daniel S. Leventhal, Kip A. West, Michela Perotti, Federica Sallusto |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Tumor microenvironment
biology Arginine Chemistry medicine.medical_treatment biology.organism_classification medicine.disease_cause lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens lcsh:RC254-282 Synthetic biology Immune system Cancer immunotherapy Blocking antibody medicine Cancer research Escherichia coli Bacteria |
| Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 8, Iss Suppl 3 (2020) |
| ISSN: | 2051-1426 |
| Popis: | Background The availability of L-arginine in tumors is a key determinant of an efficient anti-tumor T cell response. Consequently, the elevation of typically low L-arginine levels within the tumor may greatly potentiate the anti-tumor responses of immune check point inhibitors, such as PD-L1 blocking antibodies. However, currently no means are available to locally increase intra-tumoral L-arginine levels. Methods We used a synthetic biology approach to develop an engineered probiotic Escherichia coli Nissle 1917 strain that colonizes tumors and continuously converts ammonia, a metabolic waste product that accumulates in tumors, into L-arginine. Results Colonization of tumors with these bacteria elevated intra-tumoral L-arginine concentrations, increased the amount of tumor-infiltrating T cells, and had striking synergistic effects with PD-L1 blocking antibodies in the clearance of tumors. The anti-tumor effect of the living therapeutic was mediated by L-arginine and was dependent on T cells. Conclusions These results show that engineered microbial therapies enable metabolic modulation of the tumor microenvironment leading to enhanced efficacy of immunotherapies. |
| Databáze: | OpenAIRE |
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