論文 - 詳細
| RRC ID | 78958 |
|---|---|
| 著者 | Abdelmoneim M, Eissa IR, Aboalela MA, Naoe Y, Matsumura S, Sibal PA, Bustos-Villalobos I, Tanaka M, Kodera Y, Kasuya H. |
| タイトル | Metformin enhances the antitumor activity of oncolytic herpes simplex virus HF10 (canerpaturev) in a pancreatic cell cancer subcutaneous model. |
| ジャーナル | Sci Rep |
| Abstract |
Oncolytic virus (OV) therapy is a promising cancer immunotherapy, especially for cold tumors by inducing the direct lysis of cancer cells and initiation of potent antitumor response. Canerpaturev (C-REV) is an attenuated oncolytic herpes simplex virus-1, which demonstrated a potent antitumor effect in various preclinical models when used either alone or combined. Metformin is a commonly prescribed antidiabetic drug that demonstrated a potent immune modulator effect and antitumor response. We combined C-REV with metformin in a low immunogenic bilateral murine tumor model to enhance C-REV's antitumor efficacy. In vitro, metformin does not enhance the C-REV cell cytotoxic effect. However, in in vivo model, intratumoral administration of C-REV with the systemic administration of metformin led to synergistic antitumor effect on both sides of tumor and prolonged survival. Moreover, combination therapy increased the effector CD44+ CD8+ PD1- subset and decreased the proportion of terminally-differentiated CD103+ KLRG-1+ T-regulatory cells on both sides of tumor. Interestingly, combination therapy efficiently modulates conventional dendritic cells type-1 (cDC1) on tumors, and tumor-drained lymph nodes. Our findings suggest that combination of C-REV and metformin enhances systemic antitumor immunity. This study may provide insights into the mechanism of action of OV therapy plus metformin combination against various tumor models. |
| 巻・号 | 12(1) |
| ページ | 21570 |
| 公開日 | 2022-12-13 |
| DOI | 10.1038/s41598-022-25065-w |
| PII | 10.1038/s41598-022-25065-w |
| PMID | 36513720 |
| PMC | PMC9747797 |
| MeSH | Animals Cell Line, Tumor Herpesvirus 1, Human* Humans Metformin* / pharmacology Mice Oncolytic Virotherapy* Oncolytic Viruses* Pancreatic Neoplasms* / therapy |
| IF | 3.998 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Vero(RCB0001) |