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engineered E. coli Nissle 1917 (BLL strain)
- Development stage
- Preclinical
- Lead developer
- Columbia University
- Modality
- Bacterial Strains → Single Strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Yeast Strains → Single Strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Defined Consortia → Multi-strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Complex Communities → Multi-strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Fresh FMT → Fecal Microbiota Transplantation (FMT) → Microbiome Therapeutics, Frozen FMT → Fecal Microbiota Transplantation (FMT) → Microbiome Therapeutics, Genetically Modified Bacteria → Engineered Microbial Therapeutics → Microbiome Therapeutics, Synthetic Biology Platforms → Engineered Microbial Therapeutics → Microbiome Therapeutics, Microbial Metabolites → Microbiome-Derived Products → Microbiome Therapeutics, Microbial Proteins → Microbiome-Derived Products → Microbiome Therapeutics
- Administration
- Intracranial
01
Overview
Engineered E. coli Nissle 1917 (BLL strain) is an investigational live biotherapeutic product designed for the treatment of glioblastoma multiforme (GBM). Developed by researchers at Columbia University, the strain is derived from the probiotic E. coli Nissle 1917 and features a dual-layer engineering approach for safety and tumor specificity. It incorporates a biocontainment circuit (iBio) that restricts bacterial survival and proliferation to the tumor microenvironment by sensing tumor-specific cues such as hypoxia and elevated lactate levels. To further enhance safety for intracranial administration, the BLL strain is attenuated through the knockout of a membrane protein and lipopolysaccharide (LPS) components, which reduces recognition by Toll-like receptors 2 (TLR2) and 4 (TLR4), thereby minimizing neuroinflammation and toxicity. In preclinical models, the BLL strain demonstrated a 1,000-fold increase in the maximum tolerable dose compared to wild-type EcN and significantly improved survival in orthotopic glioma models.
- Other names
- engineered EcN (BLL strain)attenuated E. coli Nissle 1917
02
Targets
TLR2 (Toll-like Receptor 2)TLR4 (Toll-like receptor 4)
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