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

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

PloS one (2020-10-01)
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
ABSTRACT

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

MATERIALS
Product Number
Brand
Product Description

Millipore
FluorSave Reagent
Sigma-Aldrich
G 418 disulfate salt, powder, BioReagent, suitable for cell culture