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Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells

Tumor-derived extracellular vesicles (EVs), as tumor vaccines, carry tumor-associated antigens (TAAs), and were expected to transfer TAAs to antigen-presenting cells. However, treatment with tumor-derived EVs exhibited no obvious antitumor effect on the established tumors, likely due to their immuno...

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Autores principales: Ito, Tomoko, Sugiura, Kikuya, Hasegawa, Aya, Ouchi, Wakana, Yoshimoto, Takayuki, Mizoguchi, Izuru, Inaba, Toshio, Hamada, Katsuyuki, Eriguchi, Masazumi, Koyama, Yoshiyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824503/
https://www.ncbi.nlm.nih.gov/pubmed/33406722
http://dx.doi.org/10.3390/pharmaceutics13010057
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author Ito, Tomoko
Sugiura, Kikuya
Hasegawa, Aya
Ouchi, Wakana
Yoshimoto, Takayuki
Mizoguchi, Izuru
Inaba, Toshio
Hamada, Katsuyuki
Eriguchi, Masazumi
Koyama, Yoshiyuki
author_facet Ito, Tomoko
Sugiura, Kikuya
Hasegawa, Aya
Ouchi, Wakana
Yoshimoto, Takayuki
Mizoguchi, Izuru
Inaba, Toshio
Hamada, Katsuyuki
Eriguchi, Masazumi
Koyama, Yoshiyuki
author_sort Ito, Tomoko
collection PubMed
description Tumor-derived extracellular vesicles (EVs), as tumor vaccines, carry tumor-associated antigens (TAAs), and were expected to transfer TAAs to antigen-presenting cells. However, treatment with tumor-derived EVs exhibited no obvious antitumor effect on the established tumors, likely due to their immuno-suppressive functions, and also to the poor immunogenicity of TAAs. In order to improve the immune stimulating properties, EVs expressing a highly immunogenic bacterial antigen, 6 kDa early secretory antigenic target (ESAT-6), from Mycobacterium tuberculosis were prepared by genetically modifying the parent tumor cells with a plasmid coding for ESAT-6. Cultured B16 tumor cells were transfected with a ternary complex system consisting of pDNA, polyethylenimine (PEI), and chondroitin sulfate. The cells that were transfected with the ternary complex secreted EVs with a higher number of ESAT-6 epitopes than those transfected by a conventional DNA/PEI binary complex, due to the low cytotoxicity, and durable high expression efficiency of the ternary complex systems. The EVs presenting the ESAT-6 epitope (ESAT-EV) were collected and explored as immune modulatory agents. Dendritic cells (DCs) were differentiated from mouse bone marrow cells and incubated with ESAT-EV. After incubating with the EVs for one day, the DCs expressed a significantly higher level of DC maturation marker, CD86. The DCs treated with ESAT-EV showed a significantly improved antitumor activity in tumor-bearing mice.
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spelling pubmed-78245032021-01-24 Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells Ito, Tomoko Sugiura, Kikuya Hasegawa, Aya Ouchi, Wakana Yoshimoto, Takayuki Mizoguchi, Izuru Inaba, Toshio Hamada, Katsuyuki Eriguchi, Masazumi Koyama, Yoshiyuki Pharmaceutics Article Tumor-derived extracellular vesicles (EVs), as tumor vaccines, carry tumor-associated antigens (TAAs), and were expected to transfer TAAs to antigen-presenting cells. However, treatment with tumor-derived EVs exhibited no obvious antitumor effect on the established tumors, likely due to their immuno-suppressive functions, and also to the poor immunogenicity of TAAs. In order to improve the immune stimulating properties, EVs expressing a highly immunogenic bacterial antigen, 6 kDa early secretory antigenic target (ESAT-6), from Mycobacterium tuberculosis were prepared by genetically modifying the parent tumor cells with a plasmid coding for ESAT-6. Cultured B16 tumor cells were transfected with a ternary complex system consisting of pDNA, polyethylenimine (PEI), and chondroitin sulfate. The cells that were transfected with the ternary complex secreted EVs with a higher number of ESAT-6 epitopes than those transfected by a conventional DNA/PEI binary complex, due to the low cytotoxicity, and durable high expression efficiency of the ternary complex systems. The EVs presenting the ESAT-6 epitope (ESAT-EV) were collected and explored as immune modulatory agents. Dendritic cells (DCs) were differentiated from mouse bone marrow cells and incubated with ESAT-EV. After incubating with the EVs for one day, the DCs expressed a significantly higher level of DC maturation marker, CD86. The DCs treated with ESAT-EV showed a significantly improved antitumor activity in tumor-bearing mice. MDPI 2021-01-04 /pmc/articles/PMC7824503/ /pubmed/33406722 http://dx.doi.org/10.3390/pharmaceutics13010057 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ito, Tomoko
Sugiura, Kikuya
Hasegawa, Aya
Ouchi, Wakana
Yoshimoto, Takayuki
Mizoguchi, Izuru
Inaba, Toshio
Hamada, Katsuyuki
Eriguchi, Masazumi
Koyama, Yoshiyuki
Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells
title Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells
title_full Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells
title_fullStr Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells
title_full_unstemmed Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells
title_short Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells
title_sort microbial antigen-presenting extracellular vesicles derived from genetically modified tumor cells promote antitumor activity of dendritic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824503/
https://www.ncbi.nlm.nih.gov/pubmed/33406722
http://dx.doi.org/10.3390/pharmaceutics13010057
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