Tumor Tropism of DNA Viruses for Oncolytic Virotherapy

Abstract

Oncolytic viruses (OVs) have emerged as one of the most promising cancer immunotherapy agents that selectively target and kill cancer cells while sparing normal cells. OVs are from diverse families of viruses and can possess either a DNA or an RNA genome. These viruses also have either a natural or engineered tropism for cancer cells. Oncolytic DNA viruses have the additional advantage of a stable genome and multiple-transgene insertion capability without compromising infection or replication. Herpes simplex virus 1 (HSV-1), a member of the oncolytic DNA viruses, has been approved for the treatment of cancers. This success with HSV-1 was achievable by introducing multiple genetic modifications within the virus to enhance cancer selectivity and reduce the toxicity to healthy cells. Here, we review the natural characteristics of and genetically engineered changes in selected DNA viruses that enhance the tumor tropism of these oncolytic viruses.

Keywords: DNA virus; adenovirus; herpesvirus; oncolytic virotherapy; oncolytic virus; poxvirus; tumor tropism.

Figure 1

Oncolytic DNA virus cellular tropism. Oncolytic DNA viruses are engineered to selectively infect, replicate within, and eliminate cancer cells while sparing normal cells. Notable examples include vvDD (vaccinia virus double-deleted) and HSV-1 lacking ICP6 (infected-cell protein 6).