PMID- 33406722
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210218
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 13
IP  - 1
DP  - 2021 Jan 4
TI  - Microbial Antigen-Presenting Extracellular Vesicles Derived from Genetically 
      Modified Tumor Cells Promote Antitumor Activity of Dendritic Cells.
LID - 10.3390/pharmaceutics13010057 [doi]
LID - 57
AB  - 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.
FAU - Ito, Tomoko
AU  - Ito T
AD  - Japan Anti-Tuberculosis Association, Shin-Yamanote Hospital, Tokyo 189-0021, 
      Japan.
AD  - Department of Advanced Pathobiology, Graduate School of Life and Environmental 
      Sciences, Osaka Prefecture University, Osaka 598-8531, Japan.
AD  - Department of Immunoregulation, Institute of Medical Science, Tokyo Medical 
      University, Tokyo 160-8402, Japan.
AD  - Department of Clinical Oncology, School of Medicine, Toho University, Tokyo 
      143-8541, Japan.
FAU - Sugiura, Kikuya
AU  - Sugiura K
AUID- ORCID: 0000-0003-3366-237X
AD  - Department of Advanced Pathobiology, Graduate School of Life and Environmental 
      Sciences, Osaka Prefecture University, Osaka 598-8531, Japan.
FAU - Hasegawa, Aya
AU  - Hasegawa A
AD  - Department of Advanced Pathobiology, Graduate School of Life and Environmental 
      Sciences, Osaka Prefecture University, Osaka 598-8531, Japan.
FAU - Ouchi, Wakana
AU  - Ouchi W
AD  - Department of Advanced Pathobiology, Graduate School of Life and Environmental 
      Sciences, Osaka Prefecture University, Osaka 598-8531, Japan.
FAU - Yoshimoto, Takayuki
AU  - Yoshimoto T
AD  - Department of Immunoregulation, Institute of Medical Science, Tokyo Medical 
      University, Tokyo 160-8402, Japan.
FAU - Mizoguchi, Izuru
AU  - Mizoguchi I
AD  - Department of Immunoregulation, Institute of Medical Science, Tokyo Medical 
      University, Tokyo 160-8402, Japan.
FAU - Inaba, Toshio
AU  - Inaba T
AD  - Department of Advanced Pathobiology, Graduate School of Life and Environmental 
      Sciences, Osaka Prefecture University, Osaka 598-8531, Japan.
FAU - Hamada, Katsuyuki
AU  - Hamada K
AD  - Department of Clinical Oncology, School of Medicine, Toho University, Tokyo 
      143-8541, Japan.
FAU - Eriguchi, Masazumi
AU  - Eriguchi M
AD  - Japan Anti-Tuberculosis Association, Shin-Yamanote Hospital, Tokyo 189-0021, 
      Japan.
FAU - Koyama, Yoshiyuki
AU  - Koyama Y
AD  - Japan Anti-Tuberculosis Association, Shin-Yamanote Hospital, Tokyo 189-0021, 
      Japan.
AD  - Department of Advanced Pathobiology, Graduate School of Life and Environmental 
      Sciences, Osaka Prefecture University, Osaka 598-8531, Japan.
AD  - Department of Immunoregulation, Institute of Medical Science, Tokyo Medical 
      University, Tokyo 160-8402, Japan.
AD  - Department of Clinical Oncology, School of Medicine, Toho University, Tokyo 
      143-8541, Japan.
LA  - eng
GR  - 16K01394/Japan Society for the Promotion of Science/
GR  - 17K01390/Japan Society for the Promotion of Science/
GR  - 19K12806/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20210104
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC7824503
OTO - NOTNLM
OT  - ESAT-6
OT  - cancer immunotherapy
OT  - dendritic cells
OT  - extracellular vesicles
OT  - neoantigens
COIS- The authors declare no conflict of interest.
EDAT- 2021/01/08 06:00
MHDA- 2021/01/08 06:01
PMCR- 2021/01/04
CRDT- 2021/01/07 01:03
PHST- 2020/11/25 00:00 [received]
PHST- 2020/12/29 00:00 [revised]
PHST- 2020/12/29 00:00 [accepted]
PHST- 2021/01/07 01:03 [entrez]
PHST- 2021/01/08 06:00 [pubmed]
PHST- 2021/01/08 06:01 [medline]
PHST- 2021/01/04 00:00 [pmc-release]
AID - pharmaceutics13010057 [pii]
AID - pharmaceutics-13-00057 [pii]
AID - 10.3390/pharmaceutics13010057 [doi]
PST - epublish
SO  - Pharmaceutics. 2021 Jan 4;13(1):57. doi: 10.3390/pharmaceutics13010057.