IL-24-armed oncolytic vaccinia virus exerts potent antitumor effects via multiple pathways in colorectal cancer.

Abstract:

:Colorectal cancer is an aggressive malignancy for which there are limited treatment options. Oncolytic vaccinia virus isbeing developed as a novel strategy for cancer therapy. Arming vaccinia virus with immunostimulatory cytokines can enhance the tumor cell-specific replication and antitumor efficacy. Interleukin-24 (IL-24) is an important immune mediator, as well as a broad-spectrum tumor suppressor. Here, we constructed a targeted vaccinia virus of Guang9 strain harbored IL-24 (VG9-IL-24) to evaluate its antitumor effects. In vitro, VG9-IL-24 induced increased number of apoptotic cells and blocked colorectal cancer cells in the G2/M phase of the cell cycle. VG9-IL-24 induced apoptosis in colorectal cancer cells via multiple apoptotic signaling pathways. In vivo,VG9-IL-24 significantly inhibited the tumor growth and prolonged the survival both in human and murine colorectal cancer models. Besides, VG9-IL-24 stimulated multiple antitumor immune responses and direct bystander antitumor activity. Our results indicate that VG9-IL-24 can inhibit the growth of colorectal cancer tumor by inducing oncolysis and apoptosis as well as stimulating the anti-tumor immune effects. These findings indicate that VG9-IL-24 may exert a potential therapeutic strategy for combating colorectal cancer.

journal_name

Oncol Res

journal_title

Oncology research

authors

Deng L,Yang X,Fan J,Ding Y,Peng Y,Xu D,Huang B,Hu Z

doi

10.3727/096504020X15942028641011

subject

Has Abstract

pub_date

2020-07-08 00:00:00

eissn

0965-0407

issn

1555-3906

pub_type

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