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

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 SIIN-FEKL-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.

Ambroxol Hydrochloride Loaded Gastro-Retentive Nanosuspension Gels Potentiate Anticancer Activity in Lung Cancer (A549) Cells

“…In addition, the chitosan (CS) could enhance the general cell-mediated and humoral immunity after intestinal absorption when it became soluble at pH higher than 5. Afterward, CS could be considered as a biological modifier in the case of cancer due to the enhancement of the body immune cells (T-cells and natural killer cells) and antibody production to capture the cancer cells or the apoptotic cells after the absorbed ABX nanoparticles action [ 21 ]. The inclusion and release of the ABX were as nanoparticles from the suspension after raft/floating gel formation at the stomach.…”

Immune-regulating camouflaged nanoplatforms: A promising strategy to improve cancer nano-immunotherapy

“…Utilizing the mucosal route, chitosan-cloaked nanoplatforms can be transferred into immune-competent cells to foster cellular immune responses. By tuning the size of chitosan nanoparticles, Walter and coworkers explored the potential of chitosan nanoparticles as antigen vehicles to deliver ovalbumin-derived peptide SIINFEKL (OVA 257–264) into tumor tissue for a potent immune response [ 60 ]. It was observed that DCs could effectively take up the chitosan-based nanoparticles with small particle sizes, generally regarded as the most potent APCs to induce activation and proliferation of tumor antigen-specific CD8 + T cells.…”

“… Eliciting an antitumor immune response Immunotherapy Chitosan nanoparticles of small size were confirmed to act as suitable antigen vehicles to induce activation and proliferation of tumor antigen-specific CD8 + T cells. [ 60 ] A core-shell gold nanocage coated with manganese dioxide and HA (AMH). Evading immune elimination/tumor targeting PDT and ICD-elicited immunotherapy AMH nanoparticles with biocompatibility demonstrated targeting ability towards CD44-overexpressing cancerous cells and oxygenation-boosted immunogenic phototherapy in situ .…”

Engineering immunomodulatory nanoplatforms from commensal bacteria-derived polysaccharide A

“…61 Thus, considering the nanostructures can be made to also include antigens, the design of PSA–polymer conjugates presents an attractive for designing novel vaccines or nanotherapeutics for infectious diseases. 45,62,63 Moreover, synthetic polymers can be designed to incorporate biodegradable linkages into the backbone chain which would ensure they also undergo degradation like the carbohydrates and ensure clearance of the materials. 64 Thus, the materials can be designed to be safe and compatible with in vivo applications akin to carbohydrates.…”