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 G
2
/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.
Keywords
Cite This Article
Deng, L., Yang, X., Fan, J., Ding, Y., Peng, Y. et al. (2020). IL-24-Armed Oncolytic Vaccinia Virus Exerts Potent Antitumor Effects via Multiple Pathways in Colorectal Cancer.
Oncology Research, 28(6), 579–590.