Oncolytic Vaccinia Virus Expressing White-Spotted Charr Lectin Regulates Antiviral Response in Tumor Cells and Inhibits Tumor Growth In Vitro and In Vivo.

Xue Wang,Kan Chen,Ningning Zhou,Gongchu Li,Ting Ye,Tingting Liu,Xiaoyuan Jia

doi:10.3390/md19060292

Xue Wang, Kan Chen + Show 5 more

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https://doi.org/10.3390/md19060292

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Journal: Marine drugs	Publication Date: May 21, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Zhejiang Sci-Tech University

Abstract

Oncolytic vaccina virus (oncoVV) used for cancer therapy has progressed in recent years. Here, a gene encoding white-spotted charr lectin (WCL) was inserted into an oncoVV vector to form an oncoVV-WCL recombinant virus. OncoVV-WCL induced higher levels of apoptosis and cytotoxicity, and replicated faster than control virus in cancer cells. OncoVV-WCL promoted IRF-3 transcriptional activity to induce higher levels of type I interferons (IFNs) and blocked the IFN-induced antiviral response by inhibiting the activity of IFN-stimulated responsive element (ISRE) and the expression of interferon-stimulated genes (ISGs). The higher levels of viral replication and antitumor activity of oncoVV-WCL were further demonstrated in a mouse xenograft tumor model. Therefore, the engineered oncoVV expressing WCL might provide a new avenue for anticancer gene therapy.

Highlights

Lectins are a group of proteins that bind carbohydrates reversibly and and play important roles in various biological processes such as cell division, fertilization, congenital immunity, and cell recognition [1]
The cell viability of the oncolytic vaccinia virus (oncoVV)-white-spotted charr lectin (WCL) group was decreased compared to the oncoVV group (Figure 1a)
The results indicate that exogenous WCL expression enhanced the cytotoxicity of oncoVV in H460, PLC/PRF/5 and Huh-7 cell lines

Summary

Introduction

Lectins are a group of proteins that bind carbohydrates reversibly and and play important roles in various biological processes such as cell division, fertilization, congenital immunity, and cell recognition [1]. Lectins have shown remarkable abilities in inducing apoptosis and inhibiting angiogenesis, suggesting the future use in treating cancers [2,3]. Eucheuma serra agglutinin in red macroalga induced apoptosis in various colon adenocarcinoma, breast cancer and osteosarcoma cells [4,5,6]. Crenomytilus grayanus lectin extracted from homonymous bivalve showed globotriaosylceramide (Gb3)-dependent cytotoxicity in breast cancer and Burkitt’s lymphoma cells [7,8]. N-acetyl sugar-binding lectin isolated from Ibacus novemdentatus elicited acytotoxic effects on various cancer cells through glycoconjugate interaction [9]

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