| 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
|
| リソース情報 |
| ヒト・動物細胞 |
Vero(RCB0001) |
