Authors Kast, V. ; Nadernezhad, A. ; Pette, D. ; Gabrielyan, A. ; Fusenig, M. ; Honselmann, K.C. ; Stange, D.E. ; Werner, C. ; Loessner, D.
Title A tumor microenvironment model of pancreatic cancer to elucidate responses toward immunotherapy
Date 01.06.2023
Abstract Pancreatic cancer is a devastating malignancy with minimal treatmentoptions. Standard-of-care therapy, including surgery and chemotherapy, isunsatisfactory, and therapies harnessing the immune system have beenunsuccessful in clinical trials. Resistance to therapy and disease progressionare mediated by the tumor microenvironment, which contains excessiveamounts of extracellular matrix and stromal cells, acting as a barrier to drugdelivery. There is a lack of preclinical pancreatic cancer models thatreconstruct the extracellular, cellular, and biomechanical elements of tumortissues to assess responses toward immunotherapy. To address this limitationand explore the effects of immunotherapy in combination with chemotherapy,a multicellular 3D cancer model using a star-shaped poly(ethyleneglycol)–heparin hydrogel matrix is developed. Human pancreatic cancer cells,cancer-associated fibroblasts, and myeloid cells are grown encapsulated inhydrogels to mimic key components of tumor tissues, and cell responsestoward treatment are assessed. Combining the CD11b agonist ADH-503 withanti-PD-1 immunotherapy and chemotherapy leads to a significant reductionin tumor cell viability, proliferation, metabolic activity, immunomodulation,and secretion of immunosuppressive and tumor growth-promoting cytokines.
Journal Advanced Healthcare Materials 12 (2023) 2201907

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