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ID 62689
Author
Kakiuchi, Yoshihiko Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kuroda, Shinji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID researchmap
Kanaya, Nobuhiko Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kumon, Kento Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Tsumura, Tomoko Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hashimoto, Masashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yagi, Chiaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sugimoto, Ryoma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Hamada, Yuki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kikuchi, Satoru Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID
Nishizaki, Masahiko Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID publons
Kagawa, Shunsuke Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Tazawa, Hiroshi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Urata, Yasuo Oncolys BioPharma, Inc
Fujiwara, Toshiyoshi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Abstract
Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs.
Keywords
Extracellular vesicles
Exosome
Abscopal effect
Oncolytic adenovirus
Local treatment
Systemic delivery
Drug delivery system
Note
© 2021 The American Society of Gene and Cell Therapy. This manuscript version is made available under the CC-BY-NC-ND 4.0 License.http://creativecommons.org/licenses/by-nc-nd/4.0/.This is the accepted manuscript version. The formal published version is available at [https://doi.org/10.1016/j.ymthe.2021.05.015] .
This fulltext is available in May. 2022.
Published Date
2021-05-21
Publication Title
Molecular Therapy
Volume
volume29
Issue
issue10
Publisher
The American Society of Gene and Cell Therapy
Start Page
2920
End Page
2930
ISSN
15250016
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2021 The American Society of Gene and Cell Therapy.
File Version
author
PubMed ID
DOI
Related Url
isVersionOf https://doi.org/10.1016/j.ymthe.2021.05.015
License
http://creativecommons.org/licenses/by-nc-nd/4.0/
Citation
Yoshihiko Kakiuchi, Shinji Kuroda, Nobuhiko Kanaya, Kento Kumon, Tomoko Tsumura, Masashi Hashimoto, Chiaki Yagi, Ryoma Sugimoto, Yuki Hamada, Satoru Kikuchi, Masahiko Nishizaki, Shunsuke Kagawa, Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara, Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles, Molecular Therapy, Volume 29, Issue 10, 2021, Pages 2920-2930
Open Access (Publisher)
non-OA
Open Archive (publisher)
Non-OpenArchive