腫瘍融解アデノウイルスでの局所治療後に分泌される腫瘍由来細胞外小胞はアブスコパル効果を引き起こす
| Autor: | Nobuhiko Kanaya, Tomoko Tsumura, Ryoma Sugimoto, Toshiyoshi Fujiwara, Satoru Kikuchi, Masashi Hashimoto, Yasuo Urata, Hiroshi Tazawa, Kento Kumon, Masahiko Nishizaki, Shinji Kuroda, Yuki Hamada, Yoshihiko Kakiuchi, Chiaki Yagi, Shunsuke Kagawa |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncolytic adenovirus
Cell Survival Drug delivery system Abscopal effect Exosome Adenoviridae Extracellular Vesicles Mice Systemic delivery Cell Line Tumor Drug Discovery Genetics Cytotoxic T cell Animals Humans Molecular Biology Pharmacology Chemistry Autophagy Local treatment Liver Neoplasms Tumor-Derived HCT116 Cells Xenograft Model Antitumor Assays Oncolytic virus Oncolytic Viruses Viral Tropism Apoptosis Colonic Neoplasms Cancer research Molecular Medicine Original Article |
| Zdroj: | Mol Ther |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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