Figure 1.

Two concepts of using oncolytic virus for cancer treatment. (A) Systemically administered oncolytic viruses possess either natural tumor tropism or can be genetically modified for enhanced tumor cell transduction. High virus dose and/or repeated administration is needed for tumor penetration as majority of the virus is rapidly cleared by liver, spleen, and other organs. High oncolytic potency of the virus is beneficial and a systemic spread of infective viral progeny from one tumor to another is required for clinical efficacy. To this end, antivirus immune response needs to be hindered either by endogenous viral genes, via genetic engineering of the virus, or with concomitant immune modulatory medication. (B) Locally administered replication-competent virus creates a strong “danger signal” at tumor site and helps immune system to see tumor as a threat. Cancer cell death mediated by (some) oncolytic viruses is immunologically active phenomenon and attracts immune cells to tumors. Immune activation can be further enhanced and tailored by immune-stimulating transgenes coded by the virus. Antigen-presenting cells pick up tumor antigens released from dying cancer cells and present these antigens to T-cells in the draining lymph node. Tumor-specific CD8+ T-cells recognize and kill cancer cells in both injected and noninjected distant tumors.