Open Access

ARTICLE

IL-24-Armed Oncolytic Vaccinia Virus Exerts Potent Antitumor Effects via Multiple Pathways in Colorectal Cancer

Lili Deng^*1, Xue Yang^†1, Jun Fan^*, Yuedi Ding^*, Ying Peng^*, Dong Xu^*, Biao Huang^*‡, Zhigang Hu^†

* NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, P.R. China
† Wuxi Children’s Hospital, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, P.R. China
‡ School of Life Science, Zhejiang Sci-Tech University, Hangzhou, P.R. China

Oncology Research 2020, 28(6), 579-590. https://doi.org/10.3727/096504020X15942028641011

Abstract

Colorectal cancer is an aggressive malignancy for which there are limited treatment options. Oncolytic vaccinia virus is being 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. We constructed a targeted vaccinia virus of Guang9 strain harboring IL-24 (VG9-IL-24) to evaluate its antitumor effects. In vitro, VG9-IL-24 induced an 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. In addition, 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 antitumor immune effects. These findings indicate that VG9-IL-24 may exert a potential therapeutic strategy for combating colorectal cancer.

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