Chitosan nanoparticles as antigen vehicles to induce effective tumor specific T cell responses

• DOI: 10.1371/journal.pone.0239369
• Publication Date: 2020-09-30T17:49:19Z
• Authors: Frederik Walter; Elsa Winter; Sascha Rahn; Judith Heidland; Saskia Meier; Anna-Maria Struzek; Marcus Lettau; Lisa-Marie Philipp; Silje Beckinger; Lilli Otto; Julia Luisa Möller; Ole Helm; Daniela Wesch; Regina Scherließ; Susanne Sebens
• Keywords: Cross-Presentation

Cancer vaccinations sensitize the immune system to recognize tumor-specific antigens de novo or boosting preexisting responses. Dendritic cells (DCs) are regarded as most potent antigen presenting (APCs) for induction of (cancer) antigen-specific CD8+ T cell Chitosan nanoparticles (CNPs) used delivery vehicle have been shown improve anti-tumor This study aimed at exploring potential CNPs by assessing activation and expansion DCs subsequent cell-mediated lysis pancreatic ductal adenocarcinoma (PDAC) cells. As model ovalbumin-derived peptide SIINFEKL was chosen. Using imaging cytometry, intracellular uptake FITC-labelled three different sizes qualities (90/10, 90/20 90/50) demonstrated in pro- anti-inflammatory macrophages extents. While larger particles (90/50) impaired survival all APCs, small (90/10) were not toxic DCs. Internalization SIINFEKL-loaded but empty 90/10-CNPs promoted a pro-inflammatory phenotype indicated elevated expression cytokines. Treatment murine DC2.4 with led marked MHC-related presentation enabled potently activate SIINFEKL-specific OT-1 finally leading effective PDAC line Panc-OVA. Overall, our supports suitability induce responses tumor