Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity
| Autor: | Carey W. Gallant, Christopher Plescia, Paul F. Miller, Michael J. James, Kip A. West, Rudy Christmas, Daniel S. Leventhal, Jian-Rong Gao, Ning Li, Adam B. Fisher, Starsha Kolodziej, Munira Momin, Christopher Bergeron, Anna Sokolovska, Andres Abin-Fuentes, Jose M. Lora |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer therapy medicine.medical_treatment Science General Physics and Astronomy Antigen-Presenting Cells Computational biology Immunological memory General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Synthetic biology Mice 0302 clinical medicine Cell Line Tumor Neoplasms medicine Escherichia coli Animals Humans lcsh:Science Mice Knockout Mice Inbred BALB C Phagocytes Multidisciplinary Innate immune system Antitumor immunity business.industry food and beverages Membrane Proteins General Chemistry Immunotherapy Biocontainment Mice Inbred C57BL Sting 030104 developmental biology Drug development 030220 oncology & carcinogenesis Interferon Type I lcsh:Q Synthetic Biology business Genetic Engineering Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Vol 11, Iss 1, Pp 1-15 (2020) |
| ISSN: | 2041-1723 |
| Popis: | Synthetic biology is a powerful tool to create therapeutics which can be rationally designed to enable unique and combinatorial functionalities. Here we utilize non-pathogenic E coli Nissle as a versatile platform for the development of a living biotherapeutic for the treatment of cancer. The engineered bacterial strain, referred to as SYNB1891, targets STING-activation to phagocytic antigen-presenting cells (APCs) in the tumor and activates complementary innate immune pathways. SYNB1891 treatment results in efficacious antitumor immunity with the formation of immunological memory in murine tumor models and robust activation of human APCs. SYNB1891 is designed to meet manufacturability and regulatory requirements with built in biocontainment features which do not compromise its efficacy. This work provides a roadmap for the development of future therapeutics and demonstrates the transformative potential of synthetic biology for the treatment of human disease when drug development criteria are incorporated into the design process for a living medicine. Synthetic biology can be used to create rationally designed living therapeutics. Here the authors engineer E. coli Nissle to target STING activation in antigen presenting cells for the treatment of solid tumors and demonstrate preclinical activity in murine models. |
| Databáze: | OpenAIRE |
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