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A Tumor Microenvironment Model of Pancreatic Cancer to Elucidate Responses toward Immunotherapy.
Kast, Verena; Nadernezhad, Ali; Pette, Dagmar; Gabrielyan, Anastasiia; Fusenig, Maximilian; Honselmann, Kim C; Stange, Daniel E; Werner, Carsten; Loessner, Daniela.
Afiliación
  • Kast V; Leibniz Institute of Polymer Research Dresden e.V, Max Bergmann Centre of Biomaterials, Hohe Straße 6, 01069, Dresden, Germany.
  • Nadernezhad A; Leibniz Institute of Polymer Research Dresden e.V, Max Bergmann Centre of Biomaterials, Hohe Straße 6, 01069, Dresden, Germany.
  • Pette D; Leibniz Institute of Polymer Research Dresden e.V, Max Bergmann Centre of Biomaterials, Hohe Straße 6, 01069, Dresden, Germany.
  • Gabrielyan A; Leibniz Institute of Polymer Research Dresden e.V, Max Bergmann Centre of Biomaterials, Hohe Straße 6, 01069, Dresden, Germany.
  • Fusenig M; Leibniz Institute of Polymer Research Dresden e.V, Max Bergmann Centre of Biomaterials, Hohe Straße 6, 01069, Dresden, Germany.
  • Honselmann KC; Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, 23562, Lübeck, Germany.
  • Stange DE; Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Medical Faculty, Technical University Dresden, 01307, Dresden, Germany.
  • Werner C; Leibniz Institute of Polymer Research Dresden e.V, Max Bergmann Centre of Biomaterials, Hohe Straße 6, 01069, Dresden, Germany.
  • Loessner D; Center for Regenerative Therapies Dresden, Technical University Dresden, Fetscherstr. 105, 01307, Dresden, Germany.
Adv Healthc Mater ; 12(14): e2201907, 2023 06.
Article en En | MEDLINE | ID: mdl-36417691
Pancreatic cancer is a devastating malignancy with minimal treatment options. Standard-of-care therapy, including surgery and chemotherapy, is unsatisfactory, and therapies harnessing the immune system have been unsuccessful in clinical trials. Resistance to therapy and disease progression are mediated by the tumor microenvironment, which contains excessive amounts of extracellular matrix and stromal cells, acting as a barrier to drug delivery. There is a lack of preclinical pancreatic cancer models that reconstruct the extracellular, cellular, and biomechanical elements of tumor tissues to assess responses toward immunotherapy. To address this limitation and explore the effects of immunotherapy in combination with chemotherapy, a multicellular 3D cancer model using a star-shaped poly(ethylene glycol)-heparin hydrogel matrix is developed. Human pancreatic cancer cells, cancer-associated fibroblasts, and myeloid cells are grown encapsulated in hydrogels to mimic key components of tumor tissues, and cell responses toward treatment are assessed. Combining the CD11b agonist ADH-503 with anti-PD-1 immunotherapy and chemotherapy leads to a significant reduction in tumor cell viability, proliferation, metabolic activity, immunomodulation, and secretion of immunosuppressive and tumor growth-promoting cytokines.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Microambiente Tumoral Límite: Humans Idioma: En Revista: Adv Healthc Mater Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Microambiente Tumoral Límite: Humans Idioma: En Revista: Adv Healthc Mater Año: 2023 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Alemania