A tumor microenvironment model of pancreatic cancer to elucidate responses toward immunotherapy

Verena Kast, Ali Nadernezhad, Dagmar Pette, Anastasiia Gabrielyan, Maximilian Fusenig, Kim C. Honselmann, Daniel E. Stange, Carsten Werner, Daniela Loessner

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number2201907
Number of pages15
JournalAdvanced Healthcare Materials
Volume12
Issue number14
DOIs
Publication statusPublished - 1 Jun 2023

Keywords

  • 3D cancer models
  • CD11b agonist
  • extracellular matrix
  • hydrogels
  • immunotherapy

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