Tumor vaccination : Chitosan nanoparticles as antigen vehicles to promote tumor-directed T cell responses
Tumor vaccination is a promising approach for treatment of cancer. Tumor vaccines sensitize the immune system to tumor-specific antigens and thus enhance CD8+ T cell responses. This immune response’s potency can be increased by a strategy where nanoparticles act as vehicles leading to more efficient antigen uptake into antigen-presenting cells with chitosan emerging as a promising basic substance. In this study, the potential of antigen-loaded chitosan nanoparticles (CNPs) as delivery systems for inducing a potent CD8+ T cell response was assessed by using the model antigen SIINFEKL. First, uptake of FITC-conjugated antigen-loaded CNPs was verified. Small (approx. 200 nm in diameter) 90/10 CNPs did not show cytotoxic effects on human dendritic cells. Antigen-loaded CNPs did promote a more proinflammatory phenotype in murine and human dendritic cells. MHC-I mediated presentation of SIINFEKL on DC2.4 cells after treatment with SIINFEKL-loaded 90/10 CNPs was demonstrated. Coculturing CD8+ T cells isolated from spleens of OT-1 mice with DC2.4 cells that had been treated with SIINFEKL-loaded 90/10 CNPs led to elevation of activation marker expression on CD8+ T cells. Lastly, the functionality of these OT-1 derived CD8+ T cells activated by coculture with DC2.4 cells after pre-stimulation with 90/10 SIINFEKL CNPs was demonstrated by verifying CD8+ T cell-mediated antigen-specific lysis of PancOVA cells. Overall, the verification of internalization into dendritic cells, demonstration of low cytotoxicity and initiation of a more proinflammatory phenotype in dendritic cells, confirmation of MHC-I mediated antigen presentation and the activation of functionally active CD8+ T cells supports the hypothesis that CNPs are promising vehicles for tumor vaccination. Further studies have to be conducted to assess CNPs in a more clinical setting.