PMID- 32997691
OWN - NLM
STAT- MEDLINE
DCOM- 20201109
LR  - 20240329
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 15
IP  - 9
DP  - 2020
TI  - Chitosan nanoparticles as antigen vehicles to induce effective tumor specific T 
      cell responses.
PG  - e0239369
LID - 10.1371/journal.pone.0239369 [doi]
LID - e0239369
AB  - 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.
FAU - Walter, Frederik
AU  - Walter F
AD  - Institute for Experimental Cancer Research, Kiel University and University 
      Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany.
FAU - Winter, Elsa
AU  - Winter E
AD  - Institute for Experimental Cancer Research, Kiel University and University 
      Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany.
FAU - Rahn, Sascha
AU  - Rahn S
AD  - Institute of Biochemistry, Kiel University, Kiel, Germany.
FAU - Heidland, Judith
AU  - Heidland J
AD  - Department of Pharmaceutics and Biopharmaceutics, Kiel University, Kiel, Germany.
FAU - Meier, Saskia
AU  - Meier S
AD  - Department of Pharmaceutics and Biopharmaceutics, Kiel University, Kiel, Germany.
FAU - Struzek, Anna-Maria
AU  - Struzek AM
AD  - Department of Pharmaceutics and Biopharmaceutics, Kiel University, Kiel, Germany.
FAU - Lettau, Marcus
AU  - Lettau M
AD  - Institute of Immunology, Kiel University and UKSH Campus Kiel, Kiel, Germany.
FAU - Philipp, Lisa-Marie
AU  - Philipp LM
AD  - Institute for Experimental Cancer Research, Kiel University and University 
      Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany.
FAU - Beckinger, Silje
AU  - Beckinger S
AD  - Institute for Experimental Cancer Research, Kiel University and University 
      Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany.
FAU - Otto, Lilli
AU  - Otto L
AD  - Institute for Experimental Cancer Research, Kiel University and University 
      Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany.
FAU - Moller, Julia Luisa
AU  - Moller JL
AD  - Department of Hematology and Oncology, University Medical Center 
      Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany.
FAU - Helm, Ole
AU  - Helm O
AD  - Institute for Experimental Cancer Research, Kiel University and University 
      Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany.
FAU - Wesch, Daniela
AU  - Wesch D
AD  - Institute of Immunology, Kiel University and UKSH Campus Kiel, Kiel, Germany.
FAU - Scherliess, Regina
AU  - Scherliess R
AD  - Department of Pharmaceutics and Biopharmaceutics, Kiel University, Kiel, Germany.
FAU - Sebens, Susanne
AU  - Sebens S
AUID- ORCID: 0000-0001-6582-0083
AD  - Institute for Experimental Cancer Research, Kiel University and University 
      Medical Center Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200930
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Drug Carriers)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/*chemistry/*immunology
MH  - CD8-Positive T-Lymphocytes/cytology/*immunology
MH  - Cell Line
MH  - Chitosan/*chemistry
MH  - Coculture Techniques
MH  - Dendritic Cells/cytology/immunology
MH  - Drug Carriers/*chemistry
MH  - Humans
MH  - Mice
MH  - Nanoparticles/*chemistry
MH  - Phenotype
MH  - Vaccination
PMC - PMC7526875
COIS- R.S. is named as co-inventor in a patent application covering antigen-loaded 
      chitosan nanoparticles for immunotherapy (WO2015/185180A1). The author is not 
      employed by Merck KGaA or currently receives funding related to the patent. All 
      other authors declare no conflict of interest.
EDAT- 2020/10/01 06:00
MHDA- 2020/11/11 06:00
PMCR- 2020/09/30
CRDT- 2020/09/30 17:12
PHST- 2020/05/07 00:00 [received]
PHST- 2020/09/07 00:00 [accepted]
PHST- 2020/09/30 17:12 [entrez]
PHST- 2020/10/01 06:00 [pubmed]
PHST- 2020/11/11 06:00 [medline]
PHST- 2020/09/30 00:00 [pmc-release]
AID - PONE-D-20-13364 [pii]
AID - 10.1371/journal.pone.0239369 [doi]
PST - epublish
SO  - PLoS One. 2020 Sep 30;15(9):e0239369. doi: 10.1371/journal.pone.0239369. 
      eCollection 2020.