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

Cancers

Cari A. Young¹  Edith Zuniga²  Vic Zamloot²  Edwin R. Manuel²  Kevin B. Passi²  Lukas J. Sobocinski²  Nancy D. Ebelt²  Bruce R. Blazar³ 

[1] Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA;Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA;Department of Pediatrics, Division of Blood and Bone Marrow Transplantation, University of Minnesota Medical School, Minneapolis, MN 55455, USA;

关键词: pancreatic ductal adenocarcinoma;    targeted therapies;    therapeutic resistance;    tumor microenvironment;    desmoplasia;    collagen;   

DOI  :  10.3390/cancers13143565

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown