577 Engineered non-pathogenic synthetic biotic producing L-arginine synergize with PD-1-based cancer immunotherapy. (10th December 2020)

• Record Type: Journal Article
• Authors: Canale, Fernando; Basso, Camilla; Li, Ning; Sokolovska, Anna; Perotti, Michela; James, Michael; Jin, Wenjie; Theurillat, Jean-Philippe; Leventhal, Daniel; West, Kip; Lora, Jose; Sallusto, Federica; Geiger, Roger
• Is Part Of: Journal for immunotherapy of cancer. Volume 8(2020)Supplement 3
• Page Start: A346
• Page End: A346
• Publication Date: 2020-12-10
• Subjects: Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2020-SITC2020.0577
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : 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.