Oncolytic Vaccinia Virus Expressing Aphrocallistes vastus Lectin as a Cancer Therapeutic Agent.

Tao Wu,Yulin Xiang,Xue Wang,Gongchu Li,Tingting Liu,Ting Ye,Xiaoyuan Ren

doi:10.3390/md17060363

Abstract

Lectins display a variety of biological functions including insecticidal, antimicrobial, as well as antitumor activities. In this report, a gene encoding Aphrocallistes vastus lectin (AVL), a C-type lectin, was inserted into an oncolytic vaccinia virus vector (oncoVV) to form a recombinant virus oncoVV-AVL, which showed significant in vitro antiproliferative activity in a variety of cancer cell lines. Further investigations revealed that oncoVV-AVL replicated faster than oncoVV significantly in cancer cells. Intracellular signaling elements including NF-κB2, NIK, as well as ERK were determined to be altered by oncoVV-AVL. Virus replication upregulated by AVL was completely dependent on ERK activity. Furthermore, in vivo studies showed that oncoVV-AVL elicited significant antitumor effect in colorectal cancer and liver cancer mouse models. Our study might provide insights into a novel way of the utilization of marine lectin AVL in oncolytic viral therapies.

Highlights

Lectins, as a class of specific glycosyl-binding glycoproteins, preferentially recognize and bind carbohydrate complexes [1,2]
Lectins such as Maackia amurensis seed lectin [14], Concanavalin A [15], Fenneropenaeus indicus hemolymph fucose binding lectin [16], Polygonatum cyrtonema lectin [17], as well as MytiLec [18,19,20] were shown to be cytotoxic to cancer cells through inducing apoptosis or autophagy
To investigate the cytotoxicity of exogenously expressed Aphrocallistes vastus lectin (AVL), Ad-AVL, a non-replicating adenovirus carrying an AVL gene, was assessed by MTT assay in colorectal cancer cell line HCT116, glioma cell line U251, hepatocellular carcinoma cell lines BEL-7404, and MHCC97-H, as well as colon cancer cell line HT-29

Summary

Introduction

As a class of specific glycosyl-binding glycoproteins, preferentially recognize and bind carbohydrate complexes [1,2]. Lectins have been developed to form a variety of biological techniques, such as lectin array, lectin blot, as well as lectin-based chromatography, to analyze glycofiles and biomarkers for various cancers, including ovarian cancer [8], pancreatic cancer [9], prostate cancer [10], aggressive breast cancer [11,12], and liver cancer [13] Lectins such as Maackia amurensis seed lectin [14], Concanavalin A [15], Fenneropenaeus indicus hemolymph fucose binding lectin [16], Polygonatum cyrtonema lectin [17], as well as MytiLec [18,19,20] were shown to be cytotoxic to cancer cells through inducing apoptosis or autophagy

Methods

Results

Conclusion