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Collagenase-Expressing Salmonella Targets Major Collagens in Pancreatic Cancer Leading to Reductions in Immunosuppressive Subsets and Tumor Growth.
Ebelt, Nancy D; Zamloot, Vic; Zuniga, Edith; Passi, Kevin B; Sobocinski, Lukas J; Young, Cari A; Blazar, Bruce R; Manuel, Edwin R.
Afiliação
  • Ebelt ND; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
  • Zamloot V; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
  • Zuniga E; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
  • Passi KB; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
  • Sobocinski LJ; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
  • Young CA; Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA.
  • Blazar BR; Department of Pediatrics, Division of Blood and Bone Marrow Transplantation, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
  • Manuel ER; Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Cancers (Basel) ; 13(14)2021 Jul 16.
Article em En | MEDLINE | ID: mdl-34298778
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Cancers (Basel) Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos