Recombinant Viruses for Cancer Therapy

Abstract

Recombinant viruses are novel therapeutic agents that can be utilized for treatment of various diseases, including cancers. Recombinant viruses can be engineered to express foreign transgenes and have a broad tropism allowing gene expression in a wide range of host cells. They can be selected or designed for specific therapeutic goals; for example, recombinant viruses could be used to stimulate host immune response against tumor-specific antigens and therefore overcome the ability of the tumor to evade the host's immune surveillance. Alternatively, recombinant viruses could express immunomodulatory genes which stimulate an anti-cancer immune response. Oncolytic viruses can replicate specifically in tumor cells and induce toxic effects leading to cell lysis and apoptosis. However, each of these approaches face certain difficulties that must be resolved to achieve maximum therapeutic efficacy. In this review we discuss actively developing approaches for cancer therapy based on recombinant viruses, problems that need to be overcome, and possible prospects for further development of recombinant virus based therapy.

Keywords: cell therapy; chimeric antigen receptor (CAR) T-cell therapy; gene therapy; oncolytic viruses; recombinant viruses; virus-based vaccines.

Figure 1

Recombinant virus based treatment of cancer. (A) Antitumor therapeutic vaccines, which are based on viruses encoding tumor-specific antigens, boost anti-cancer immune responses by enhanced presentation of the tumor antigens to immune cells. Another promising approach is the use of immune cell-based vaccines to stimulate antitumor immunity. In this case, T-cells are genetically engineered to express tumor-specific antigen receptors to improve recognition of cancer cells, for example CARs. (B) Therapeutic viruses, for example MV-NIS (the Edmonston strain of measles virus), can also be delivered to the tumor with mesenchymal stem cells (MSCs), which have a natural tropism toward tumor niches. (C) Oncolytic viruses preferentially infect tumor cells and induce tumor cell death. Additional genetic modification with immunomodulating genes such as granulocyte-macrophage colony-stimulating factor (GM-CSF), can enhance anti-tumor effect. Oncolytic viruses also cause local inflammation, which manifests as increased infiltration of immune cells into the tumor, local release of interferons (IFNs), chemokines, danger-associated molecular patterns (DAMPs), pathogen-associated molecular patterns (PAMPs) and mediate a tumor-specific immune response.