Medically reviewed by Prof. Shimon Slavin, MD. Updated: March 2026
Oncolytic virus therapy is a form of cancer immunotherapy that uses viruses to selectively infect and destroy tumor cells while stimulating anti-tumor immune responses. This approach, sometimes referred to as oncolytic virotherapy, is considered a promising approach in modern cancer treatment.
What are oncolytic viruses
Oncolytic viruses are a unique class of viruses capable of selectively destroying cancer cells while largely sparing normal tissues. Because many tumor cells have impaired antiviral defense mechanisms, these viruses can replicate inside malignant cells much more efficiently than in healthy tissue.
How Oncolytic Virus Therapy Works
Understanding how oncolytic virus therapy works requires examining the biological mechanisms that allow certain viruses to selectively infect and destroy tumor cells. Cancer cells often have impaired antiviral defense mechanisms, including defects in interferon signaling pathways and abnormal regulation of cellular immunity. These biological abnormalities make many tumors particularly vulnerable to infection by oncolytic viruses and form the scientific basis of oncolytic virus therapy.
The mechanism of action of oncolytic viruses involves several interrelated biological processes. The most important of these include direct destruction of tumor cells (lysis), activation of the innate immune response, and stimulation of adaptive antitumor immunity.
- Direct Cancer Cell Lysis
- Innate Immune Response
- Adaptive Immune Response
1. Direct Cancer Cell Lysis
Oncolytic viruses directly kill cancer cells by entering the cell and using the cell’s machinery to replicate. As the virus replicates, it causes the cancer cell to burst open (lysis), releasing new virus particles into the surrounding tissue. This process destroys the cancer cell and can trigger an immune response, making the body more capable of recognizing and attacking the surrounding cancer cells. Direct destruction of malignant cells therefore represents one of the key mechanisms that make oncolytic virus therapy a promising approach in cancer treatment.
2. Innate Immune Response
The innate immune system represents the body’s first line of defense against viral infection. Oncolytic viruses infect tumor cells, leading to the release of signaling molecules, including cytokines, chemokines, and interferons. These molecules activate immune cells and trigger an inflammatory response in the tumor area. Oncolytic viruses stimulate innate immune cells, including:
Natural Killer (NK) Cells
NK cells play a key role in the innate antitumor immune response. Through specialized receptors, NK cells are able to recognize infected or abnormal cells and destroy them.
Dendritic Cells (DC) and Macrophages
Oncolytic viruses help destroy cancer cells and release tumor-associated antigens — fragments of tumor proteins. Dendritic cells and macrophages capture these antigens, process them, and present them to T- and B-lymphocytes. This activates the lymphocytes, which learn to recognize and destroy cancer cells, enhancing the overall antitumor immune response.
3. Adaptive Immune Response
The adaptive immune response is the part of the immune system activated upon encountering foreign agents. It is more specific and aimed at combating particular threats. The process involves T-lymphocytes, which destroy infected cells, and B-lymphocytes, which produce antibodies. Adaptive immunity also forms immunological memory, enabling the body to respond rapidly to repeated infections or cancer cells.
As a result, the immune system begins to recognize tumor cells more effectively, creating a systemic anti-tumor immune response that may extend beyond the initially infected tumor site.
Which Oncolytic Viruses Are Used in Cancer Treatment
Several types of oncolytic viruses are currently being studied in clinical trials and cancer immunotherapy research. These viruses differ in their biological properties, tumor selectivity, and mechanisms of immune activation. Oncolytic viruses used in cancer research belong to several biological virus families.
- Newcastle Disease Virus (NDV)
- Infectious Bursal Disease Virus (IBDV)
- Adenoviruses
- Herpes Simplex Virus (HSV-1, e.g. T-VEC)
- Reovirus
In our clinical practice, we use two types of oncolytic viruses, characterized by selective activity against tumor cells while largely sparing healthy tissue.
IBDV (Infectious Bursal Disease Virus)
IBDV is a virus that can infect tumor cells and induce their destruction, including through disruption of cellular metabolism and induction of apoptosis. Several studies have shown that IBDV may preferentially affect malignant cells, which makes it a promising subject of investigation in different types of cancer, including metastatic disease.
NDV (Newcastle Disease Virus)
Newcastle disease virus (NDV) is one of the most extensively studied oncolytic viruses. Several studies have shown that NDV is capable of infecting tumor cells and stimulating an antitumor immune response. In our clinical practice, we use a strain of Newcastle disease virus that was tested in 2017 and has demonstrated the ability to effectively infect tumor cells.
Which Cancers Can Be Treated with Oncolytic Virus Therapy
Oncolytic virus therapy is actively being studied and applied within experimental treatment approaches for various types of cancer, including:
- Brain cancer (e.g., glioblastoma, astrocytoma)
- Breast cancer
- Lung cancer
- Colorectal cancer
- Melanoma
- Pancreatic cancer
- Stomach cancer
- Cervical cancer
- Sarcomas
How Oncolytic Virus Therapy Is Administered
Oncolytic virus therapy may be administered in different ways depending on the type of tumor, its location, and the selected treatment protocol. Treatment is carried out according to an individualized protocol determined by the tumor type, stage of disease, and the patient’s overall condition. In clinical practice, both systemic and local methods of virus administration are used, as well as their combinations:
- Intravenously (via infusion)
- Intratumorally (direct injection into the tumor)
- Intranasally (via the nose)
- Via an Ommaya reservoir (for delivery to brain tumors)
Who Is a Candidate for Oncolytic Virus Therapy
Oncolytic virus therapy may be considered for patients with various solid tumors. In many cases, standard treatments such as surgery, chemotherapy, or radiation therapy are first used to reduce tumor burden, after which oncolytic virus therapy may be considered.
This approach may also be used when a tumor has developed resistance to chemotherapy or other forms of standard treatment. The decision to administer therapy is made on an individual basis following a review of the patient’s medical data, including tumor type, disease stage, and prior treatment history.
Oncolytic Viruses in Combination with Other Immunotherapy Approaches
Oncolytic virus therapy may be used not only as a standalone treatment but also in combination with other immunotherapy approaches aimed at enhancing the body’s anti-tumor immune response.
Oncolytic Viruses with Checkpoint Inhibitors
After completing a course of oncolytic virus therapy, immune checkpoint inhibitors may be considered as the next stage of treatment. This sequential approach is based on the characteristics of their immune mechanisms: early immune activation during simultaneous administration may reduce the effectiveness of viral therapy. In this strategy, viral therapy increases the visibility of tumor cells to the immune system, while checkpoint inhibitors help overcome tumor-induced immune suppression. As an alternative to checkpoint inhibitor drugs, cytokine-mediated immunotherapy (CMI) may also be considered.
Oncolytic Viruses and Anti-Cancer Vaccines
The combination of oncolytic virus therapy and anti-cancer vaccines is actively being studied and is considered a promising therapeutic approach. Oncolytic viruses induce the destruction of tumor cells and the release of tumor antigens, while an anti-cancer vaccine created from the patient’s own tumor tissue may help the immune system recognize these antigens and mount a stronger, more targeted immune response against cancer cells.
Potential Benefits of Oncolytic Virus Therapy
- May help target residual tumor cells after standard treatment
- May have activity in tumors resistant to chemotherapy
- Can be combined with other immunotherapy approaches
- Is generally well tolerated in many patients
- May be applicable to various solid tumor types
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