Effects of an Attenuated Coxsackievirus B3 Strain to Cells With Different Expression Levels of Coxsackievirus-Adenovirus Receptor

Abstract

Abstract Oncolytic therapy has emerged as a new method of cancer treatment next to surgery, chemotherapy, and radiotherapy. RNA viruses can become oncolytic viruses as their replication occurs in the cytoplasm and they do not integrate into the host DNA. Coxsackievirus can potentially become a type of oncolytic virus because of its ability to cause disease (mainly in children) and its simple genome structure which makes genetic manipulation easy. Coxsackievirus B3 (CVB3) has a good cytotoxic effect on non-small cell lung cancer in vitro. At present, some locally injectable oncolytic viruses approved for clinical studies include Rigvir and CAVATAK. Nevertheless, not enough studies are available on whether CVB3 has different cytotoxic effects on Coxsackievirus-Adenovirus Receptor (CAR) cells and whether the inhibition rate of tumor tissues show variations with different CAR expression levels in vivo. In the current research, the recombinant CVB3 strain constructed and preserved in our laboratory was used as an oncolytic virus to investigate if its cytotoxic effect on lung cancer cells was related to CAR receptor expression. Because the recombinant CVB3 strain was targeted for oncolytic treatment of lung cancer, an intravenous injection was proposed. The results indicated that the expression level of CAR on the cell surface was not the only factor affecting CVB3 infection, but the sensitivity of NSCLC cell lines to CVB3 was associated with CAR expression level on the cell surface. According to in vivo studies, the CVB3 showed a better inhibitory effect on tumor tissues that have a high level of CAR expression. These findings support the intravenous administration of CVB3 for oncolytic therapy.