Collagenase-Expressing Salmonella Targets Major Collagens in Pancreatic Cancer Leading to Reductions in Immunosuppressive Subsets and Tumor Growth

Abstract

Therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC) can be attributed, in part, to a dense extracellular matrix containing excessive collagen deposition. Here, we describe a novel Salmonella typhimurium (ST) vector expressing the bacterial collagenase Streptomyces omiyaensis trypsin (SOT), a serine protease known to hydrolyze collagens I and IV, which are predominantly found in PDAC. Utilizing aggressive models of PDAC, we show that ST-SOT selectively degrades intratumoral collagen leading to decreases in immunosuppressive subsets, tumor proliferation and viability. Ultimately, we found that ST-SOT treatment significantly modifies the intratumoral immune landscape to generate a microenvironment that may be more conducive to immunotherapy.