Polymer nanoparticles for cross-presentation of exogenous antigens and enhanced cytotoxic T-lymphocyte immune response

Song, Chanyoung; Noh, Young-Woock; Lim, Yong Taik

doi:10.2147/ijn.s110796

Cited by 52 publications

(13 citation statements)

References 30 publications

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“…As potential vaccine carriers, NPs could enhance antigen cross-presentation of DCs, thereby produce stronger antitumor immunity. For example, as shown in both in vivo and in vitro experiments, treatment with polymer NPs such as γ-PGA NPs ( 114 , 115 ), PLGA NPs ( 116 ), polyethyleneimine NPs ( 117 ) and poly(propylene sulfide) NPs ( 52 ) promoted OVA-mediated cross-presentation in DCs by different mechanisms. Changing size and surface chemistry of NPs were effective ways to regulate their effects on antigen cross-presentation intensity of DCs ( 118 , 119 ).…”

Section: Nps Affect DC Functionsmentioning

confidence: 97%

Interactions Between Nanoparticles and Dendritic Cells: From the Perspective of Cancer Immunotherapy

et al. 2018

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Dendritic cells (DCs) are the primary antigen-presenting cells and play key roles in the orchestration of the innate and adaptive immune system. Targeting DCs by nanotechnology stands as a promising strategy for cancer immunotherapy. The physicochemical properties of nanoparticles (NPs) influence their interactions with DCs, thus altering the immune outcome of DCs by changing their functions in the processes of maturation, homing, antigen processing and antigen presentation. In this review, we summarize the recent progress in targeting DCs using NPs as a drug delivery carrier in cancer immunotherapy, the recognition of NPs by DCs, and the ways the physicochemical properties of NPs affect DCs' functions. Finally, the molecular pathways in DCs that are affected by NPs are also discussed.

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Section: Nps Affect DC Functionsmentioning

confidence: 97%

Interactions Between Nanoparticles and Dendritic Cells: From the Perspective of Cancer Immunotherapy

et al. 2018

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“…It has been already demonstrated by other groups, that cross-presentation of exogenous OVA antigens by DCs occurs rapidly, which was determined e.g. between 6 and 16 hours [72][73][74]. The strong decline in H-2Kb-bound SIINFEKL presentation in DC2.4 cells after 24 hours might be explained by the lack of further maturation stimuli (e.g.…”

Section: Discussionmentioning

confidence: 76%

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

et al. 2020

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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.

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“…We observed proliferation of CD8 + T cells, but the percentages of Ki67 + cells within this CD8 + T cell pool is low due to the fact that the majority of the T cells in the co-culture is still unspecific for the CMVpp65 peptide. Previous studies have demonstrated that nanoparticle-mediated delivery of antigens can dramatically enhance and sustain exogenous antigen presentation by MHC class I [38,39]. In a previous study, we already demonstrated in vitro that encapsulation of poly(I:C) or/and CpG together with an MHC class II restricted model antigen is suitable for the induction of a CD4 + T cell response [20].…”

Section: Discussionmentioning

confidence: 95%

Effective Activation of Human Antigen-Presenting Cells and Cytotoxic CD8+ T Cells by a Calcium Phosphate-Based Nanoparticle Vaccine Delivery System

et al. 2020

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The ability of vaccines to induce T cell responses is crucial for preventing diseases caused by viruses. Nanoparticles (NPs) are considered to be efficient tools for the initiation of potent immune responses. Calcium phosphate (CaP) NPs are a class of biodegradable nanocarriers that are able to deliver immune activating molecules across physiological barriers. Therefore, the aim of this study was to assess whether Toll-like receptor (TLR) ligand and viral antigen functionalized CaP NPs are capable of inducing efficient maturation of human antigen presenting cells (APC). To achieve this, we generated primary human dendritic cells (DCs) and stimulated them with CpG or poly(I:C) functionalized CaP NPs. DCs were profoundly stronger when activated upon NP stimulation compared to treatment with soluble TLR ligands. This is indicated by increased levels of costimulatory molecules and the secretion of proinflammatory cytokines. Consequently, coculture of NP-stimulated APCs with CD8 + T cells resulted in a significant expansion of virus-specific T cells. In summary, our data suggest that functionalized CaP NPs are a suitable tool for activating human virus-specific CD8 + T cells and may represent an excellent vaccine delivery system.

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Polymer nanoparticles for cross-presentation of exogenous antigens and enhanced cytotoxic T-lymphocyte immune response

Cited by 52 publications

References 30 publications

Interactions Between Nanoparticles and Dendritic Cells: From the Perspective of Cancer Immunotherapy

Interactions Between Nanoparticles and Dendritic Cells: From the Perspective of Cancer Immunotherapy

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

Effective Activation of Human Antigen-Presenting Cells and Cytotoxic CD8+ T Cells by a Calcium Phosphate-Based Nanoparticle Vaccine Delivery System

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