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Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity.

Nature communications (2020-06-03)
Daniel S Leventhal, Anna Sokolovska, Ning Li, Christopher Plescia, Starsha A Kolodziej, Carey W Gallant, Rudy Christmas, Jian-Rong Gao, Michael J James, Andres Abin-Fuentes, Munira Momin, Christopher Bergeron, Adam Fisher, Paul F Miller, Kip A West, Jose M Lora
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Chloramphenicol, ≥98% (HPLC)
Sigma-Aldrich
LB Broth with agar (Lennox), Highly-referenced microbial growth powder medium with Agar, low salt, suitable for salt-sensitive E. coli culture.
Sigma-Aldrich
Thymidine, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Streptomycin sulfate salt, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
2,6-Diaminopimelic acid, ≥98% (TLC)
BeadBug prefilled tubes, 2.0 mL capacity, with 2.8 mm stainless steel beads, acid washed