Oncolytic activity of a coxsackievirus B3 strain in human endometrial cancer cell lines

Yanzhen Lin,Junkai Wan,Wei Wang,Tong Cheng,Dequan Pan,Linli Cai,Wenkun Fu,Xiumin Huang,Yifeng Wang,Ying Yang

doi:10.1186/s12985-018-0975-x

Abstract

BackgroundEndometrial cancer (EC) is one of the most common gynecological malignancies globally. Although progress has been made in surgical and other adjuvant therapies, there is still a great need to develop new approaches to further reduce the incidence and mortality of EC. Oncolytic virotherapy offers a novel promising option of cancer treatment and has demonstrated good efficacy in preclinical models and clinical trials. However, only few oncolytic viruses have been tested for EC treatment. In this study, the potential of an oncolytic coxsackievirus B3 (CV-B3) strain 2035A (CV-B3/2035A) was investigated as a novel biotherapeutic agent against EC.MethodsHuman EC cell lines (Ishikawa, HEC-1-A and HEC-1-B) were infected with CV-B3/2035A, and viral replication and cytotoxic effects were evaluated in vitro. CV-B3/2035A-induced oncolysis was also investigated in nude mice bearing EC xenografts in vivo and in patient-derived EC samples ex vivo.ResultsHuman EC cell lines expressing different levels of CAR and DAF were all susceptible to infection by CV-B3/2035A and supported efficient viral replication in vitro. In the EC xenograft/nude mouse model, both intratumoral and intravenous administrations of CV-B3-2035A exerted significant therapeutic effects against pre-established EC tumors without causing significant treatment-related toxicity and mortality in nude mice. Moreover, CV-B3/2035A treatment resulted in decreased viability of patient-derived EC samples ex vivo.ConclusionsCV-B3/2035A showed oncolytic activity in human EC cell lines both in vitro and in vivo as well as in patient-derived EC samples ex vivo and thus could be used as an alternative virotherapy agent for the treatment of EC.

Highlights

Endometrial cancer (EC) is one of the most common gynecological malignancies globally
Oncolytic activity of coxsackievirus B3 (CV-B3)/2035A in human EC cell lines in vitro CV-B3 2035A strain was isolated from a throat swab of an HFMD patient in Xiamen, China in 2008
A phylogenetic tree was constructed for CV-B3/2035A and 42 other CVB3 strains based on the whole genome sequences (Fig. 1)

Summary

Introduction

Endometrial cancer (EC) is one of the most common gynecological malignancies globally. Oncolytic virotherapy offers a novel promising option of cancer treatment and has demonstrated good efficacy in preclinical models and clinical trials. Oncolytic viruses are thought to exert antitumor effects by inducing selective tumor cell death, Lin et al Virology Journal (2018) 15:65 which directly eliminates viable tumor cells and sets the stage for initiation of systemic anti-tumor immune responses. Targeting of these viruses to cancer cells is mainly based on the overexpression of viral entry receptors on tumor cells and aberrant signaling pathways within tumor cells. Only few oncolytic viruses have been tested for EC treatment

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