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YS-HepIII
- Development stage
- Preclinical
- Lead developer
- City of Hope
- Modality
- Synthetic Biology Platforms → Engineered Microbial Therapeutics → Microbiome Therapeutics, Fresh FMT → Fecal Microbiota Transplantation (FMT) → Microbiome Therapeutics, Yeast Strains → Single Strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Bacterial Strains → Single Strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Defined Consortia → Multi-strain Products → Live Biotherapeutic Products → Microbiome Therapeutics, Frozen FMT → Fecal Microbiota Transplantation (FMT) → Microbiome Therapeutics, Genetically Modified Bacteria → Engineered Microbial Therapeutics → Microbiome Therapeutics, Microbial Metabolites → Microbiome-Derived Products → Microbiome Therapeutics, Microbial Proteins → Microbiome-Derived Products → Microbiome Therapeutics, Complex Communities → Multi-strain Products → Live Biotherapeutic Products → Microbiome Therapeutics
01
Overview
YS-HepIII is an engineered microbial therapy consisting of an attenuated strain of *Salmonella typhimurium* (YS1646) designed to express bacterial heparinase III (HepIII) derived from *Bacteroides*. Developed by researchers at the City of Hope, this therapeutic approach targets heparan sulfate proteoglycans (HSPG) within the tumor microenvironment, specifically for the treatment of pancreatic ductal adenocarcinoma (PDAC). Unlike mammalian heparanase, which promotes tumor progression and treatment resistance, bacterial HepIII cleaves heparan sulfate chains in a manner that deactivates HSPG signaling. This enzymatic activity leads to reduced macropinocytosis, lipid storage depletion, and decreased survival signaling in tumor cells, thereby sensitizing tumors to standard cancer therapies. The expression of HepIII is controlled by an inducible system to ensure that the enzyme is produced primarily within tumor tissue, minimizing potential systemic toxicities.
- Other names
- Salmonella typhimurium YS1646 expressing bacterial heparinase III
02
Targets
HSPG (Basement membrane-specific heparan sulfate proteoglycan core protein (perlecan))
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