Coxsackievirus B3—Its Potential as an Oncolytic Virus

Abstract

Oncolytic virotherapy represents one of the most advanced strategies to treat otherwise untreatable types of cancer. Despite encouraging developments in recent years, the limited fraction of patients responding to therapy has demonstrated the need to search for new suitable viruses. Coxsackievirus B3 (CVB3) is a promising novel candidate with particularly valuable features. Its entry receptor, the coxsackievirus and adenovirus receptor (CAR), and heparan sulfate, which is used for cellular entry by some CVB3 variants, are highly expressed on various cancer types. Consequently, CVB3 has broad anti-tumor activity, as shown in various xenograft and syngeneic mouse tumor models. In addition to direct tumor cell killing the virus induces a strong immune response against the tumor, which contributes to a substantial increase in the efficiency of the treatment. The toxicity of oncolytic CVB3 in healthy tissues is variable and depends on the virus strain. It can be abrogated by genetic engineering the virus with target sites of microRNAs. In this review, we present an overview of the current status of the development of CVB3 as an oncolytic virus and outline which steps still need to be accomplished to develop CVB3 as a therapeutic agent for clinical use in cancer treatment.

Coxsackievirus Group B3 Has Oncolytic Activity against Colon Cancer through Gasdermin E-Mediated Pyroptosis

“…This suggests that intratumorally injected CVB3 may have spread, causing myocarditis or pancreatitis. This may have been because CVB3 can infect normal cells as well, which also express the coxsackievirus and adenovirus receptor (CAR) [ 30 ]. CVB3 infection is associated with severe illness in infants; however, in adults CVB3 generally induces mild self-limiting disease with flu-like symptoms [ 30 ].…”

“…This may have been because CVB3 can infect normal cells as well, which also express the coxsackievirus and adenovirus receptor (CAR) [ 30 ]. CVB3 infection is associated with severe illness in infants; however, in adults CVB3 generally induces mild self-limiting disease with flu-like symptoms [ 30 ]. Moreover, the immune system in the healthy human body is complete, so the side-effects caused by intratumoral injection of CVB3 may be mild [ 31 ].…”

“…After the oncolytic virus infects cancer cells, it changes the tumor microenvironment, stimulating the antiviral components of the immune system which kill tumor cells. Activation of systemic immunity inhibits tumor spread and prevents recurrence [ 30 , 35 ]. Previous studies have also revealed the high potential efficacy of WT-CVB3 and genetically engineered CVB3 against metastatic colon cancer [ 10 , 11 ].…”

Virotherapy in Germany—Recent Activities in Virus Engineering, Preclinical Development, and Clinical Studies

“…Importantly, virus replication in tumors remained unaffected, and tumor growth was significantly inhibited [ 52 , 53 ]. Currently, the group is also investigating anti-tumoral immune mechanisms induced by PD, and they aim to increase the oncolytic activity of PD further by tumor cell-specific adaptation of the virus and by insertion of immunomodulatory transgenes into the viral genome [ 81 ].…”

Application Route and Immune Status of the Host Determine Safety and Oncolytic Activity of Oncolytic Coxsackievirus B3 Variant PD-H

“…Between the NTRs, the CVB3 genome encodes for a single continuous polyprotein. After translation this protein is proteolytically processed into four structural proteins (VP1 to VP4) which form the viral shell and into three nonstructural precursors (2BC, 3AB, 3CD) and seven further processed proteins (2A-2C; 3A-3D) which are required for distinct functions in the viral life cycle, such as processing of the viral protein and replication of the viral genome [6].…”