The discovery and development of oncolytic viruses: are they the future of cancer immunotherapy?

Abstract

Introduction: Despite diverse treatment modalities and novel therapies, many cancers and patients are not effectively treated. Cancer immunotherapy has recently achieved breakthrough status yet is not effective in all cancer types or patients and can generate serious adverse effects. Oncolytic viruses (OVs) are a promising new therapeutic modality that harnesses virus biology and host interactions to treat cancer. OVs, genetically engineered or natural, preferentially replicate in and kill cancer cells, sparing normal cells/tissues, and mediating anti-tumor immunity.Areas covered: This review focuses on OVs as cancer therapeutic agents from a historical perspective, especially strategies to boost their immunotherapeutic activities. OVs offer a multifaceted platform, whose activities are modulated based on the parental virus and genetic alterations. In addition to direct viral effects, many OVs can be armed with therapeutic transgenes to also act as gene therapy vectors, and/or combined with other drugs or therapies.Expert opinion: OVs are an amazingly versatile and malleable class of cancer therapies. They tend to target cellular and host physiology as opposed to specific genetic alterations, which potentially enables broad responsiveness. The biological complexity of OVs have hindered their translation; however, the recent approval of talimogene laherparepvec (T-Vec) has invigorated the field.

Keywords: Cancer; clinical trials; immunotherapy; immunovirotherapy; oncolytic virus.

Figure 1.

Historical timeline of oncolytic viruses and immunotherapy used for cancer treatment, with preclinical (blue box) and clinical (green box) highlights.

Figure 2. Schematic illustration of the mechanisms of OVs for cancer therapy.

OVs can directly destroy cancer cells (oncolysis) and tumor-associated endothelial cells, which leads to tumor mass reduction and vascular collapse. The killed tumor cells release DAMPs and tumor-associated antigens that are presented to T cells and induce anti-tumor immunity. Lastly, OVs can be armed to express different transgenes that target non-infected cells and improve immunovirotherapy.