Summary of Research and Development Progress of Oncolytic Viruses

Review Article

Austin Med Sci. 2023; 8(1): 1075.

Summary of Research and Development Progress of Oncolytic Viruses

Pengpeng Tian1,2*; Honghong Lu2,3

¹Institute of Bioengineering, Biotech Pharma Ltd, Beijing, China

²College of Science and Technology, Beijing Open University, Beijing, China

³College of Business, Beijing Open University, Beijing, China

*Corresponding author: Pengpeng Tian Institute of Bioengineering, Biotech Pharma Ltd, Rongjing East Street, Beijing Development Are (BDA), Beijing 100176, Beijing, China. Email: [email protected]

Received: April 12, 2022 Accepted: May 11, 2022 Published: May 18, 2023


Oncolytic viruses are viruses that have been genetically modified to specifically infect and kill cancer cells. They have significant potential in the field of cancer therapy because they possess many advantages over traditional treatments, such as selective killing of tumor cells, increasing the immunogenicity of tumor cells, and avoiding the side effects of chemotherapy and radiotherapy. Currently, several oncolytic viruses have shown good safety and efficacy in clinical trials. More combination therapy strategies are being explored, and it is expected that oncolytic viruses will be more widely used in cancer treatment in the future.

Keywords: Oncolytic viruses; Research and development progress; Immunotherapy


Oncolytic Viruses (OVs) are currently a hot topic among researchers and have potential anti-tumor value. In 1999, Rabkin and colleagues discovered an Oncolytic Herpes Simplex Virus (oHSV) with tumor lysing activity that acted as an in situ tumor vaccine, activating anti-tumor immunity. This study found that OV delivery and tumor cell killing led to the generation of tumor-specific CD8+T cells. Subsequent studies have shown that tumor antigen-specific adaptive immunity plays an important role in OV-mediated tumor therapy. Based on these data, scientists believe that OVs have potential value as therapeutic tumor vaccines or as a new form of immunotherapy.

Characteristics of Oncolytic Viruses

Oncolytic Viruses (OVs) are a large group of viruses with anti-tumor effects. They selectively infect tumor cells and their stroma, replicate within them, and lyse the infected cells upon completion of replication. OVs do not infect or damage normal cells or tissues for the following reasons: 1) virus-specific receptors mediate virus-specific entry into tumor cells and their stroma; 2) compared to quiescent normal cells, tumor cells have high metabolic and replicative activity, which is advantageous for virus replication; 3) the tumor-driving mutations provide a natural selection advantage for virus replication. After tumor cells and their stroma are lysed by OVs, the newly replicated viruses continue to infect other tumor cells and their stroma [1].

Classification of Oncolytic Viruses

OVs viruses can be divided into two types: natural OVs and genetically engineered OVs. Genetically engineered OVs have enhanced cell toxicity and immune activation activity. Reovirus and vaccinia virus target tumor cells naturally through the Ras signaling pathway. Reovirus selectively replicates in Ras-activated cells, while vaccinia virus tends to replicate in cells with overexpressed EGFR, as it requires EGFR-Ras signaling for replication. Genetically engineered vaccinia virus, Pexa-Vec (JX-594), targets tumor cells through multiple mechanisms, including the EGFR/KRAS signaling pathway, the level of Thymidine Kinase (TK), and the resistance of tumor cells to type 1 interferon, which can activate viral replication. Vesicular Stomatitis Virus (VSV) can infect and destroy the tumor vascular system (without damaging the normal tissue vascular system), which is critical in the treatment of solid tumors.

Mechanisms of Oncolytic Virus Killing Tumor Cells

Oncolytic Viruses (OVs) kill tumor cells and inhibit tumor progression through four mechanisms: 1) lysis. OVs replicate inside tumor cells and ultimately cause tumor cell lysis; 2) Anti-tumor immunity. The virus, tumor antigens, and lysed cell debris are presented by Dendritic Cells (DCs) to activate local and systemic immunity; 3) Destruction of tumor tissue blood vessels, which can play an important role in solid tumor treatment; and 4) expression of transgenic products. Genetic engineering modifies OVs to load target genes, increase the expression of transgenic products, and enhance the killing function of OVs against tumor cells.

OVs also have the function of regulating the Tumor MicroEnvironment (TME), which can convert “cold tumors” into “hot tumors.” This is due to the release of Damage-Associated Molecular Patterns (DAMPs) and Pathogen-Associated Molecular Patterns (PAMPs) during the infection process, the production of cytokines, the infiltration of immune cells, the induction of Immunogenic Cell Death (ICD) of tumor cells, the activation of infiltrating immune cells, and the generation of anti-tumor immunity. To further enhance the immune activation function of OVs, the following methods can be considered: 1) Integrating immune activation genes (such as Th1 cytokine coding genes) into the virus carrier. Th1 cytokines include GM-CSF and IL-2. IL-10 can act as both a Th2 cytokine and a Th1 cytokine, enhancing anti-tumor immunity. IL-24 is a member of the IL-10 family and has potential anti-tumor activity when expressed by OVs. Zhu et al. showed that vaccinia virus (one of the OVs) expressing IL-2, IL-12, IL-15, IL-21, IL-23, and IL-36γ was safe and effective in multiple tumor models. OVs expressing IL-7 and IL-12 also have anti-tumor immune activation function; 2) Integrating ICOS ligand to enhance immune cell co-stimulation in TME. OVs can upregulate the expression of T cell ICOS receptors, theoretically amplifying anti-tumor immunity; 3) Integrating Immune Checkpoint Inhibitors (ICIs) to activate anti-tumor immunity; 4) Loading CD24 and CD47 antibodies. CD24 and CD47 are “do not eat me” signals of tumor cells, which allow them to escape immune inspection and clearance. CD24 and CD47 antibodies combined with OVs can enhance innate immunity, improve lysing function, and further promote immune regulation; 5) Loading tumor antigens to induce antigen-specific CD8+ CTL response; 6) Loading signaling pathway inhibitors to avoid the interaction between tumor cells and TME. The CXCR4/CXCR12 signal is blocked by CXCR4 antagonists to destroy tumor vascular tissue, induce ICD, reverse immune suppression in TME, enhance anti-tumor immunity, and inhibit tumor metastasis. 7) Loading T cell “engagers” to link initial T cells and tumor cells, activate T cells without the need for MHC, and eliminate tumor cells [2].