Oncolytic viruses are a unique class of viruses capable of destroying cancer cells while avoiding damage to healthy tissues. Although research on this treatment began in the 1960s, clinical application only became feasible in recent years. Today, oncolytic viruses are among the most promising and actively researched approaches in cancer immunotherapy.
How Do Oncolytic Viruses Work?
Oncolytic viruses exploit vulnerabilities in cancer cells that lack effective antiviral defenses. Unlike healthy cells, cancer cells are unable to activate normal antiviral mechanisms, making them ideal targets. These viruses are designed to recognize specific molecules on the surface of tumor cells, allowing them to penetrate and destroy the cancer cells while leaving healthy tissues unaffected. Oncolytic viruses fight cancer in two main ways: by directly destroying cancer cells and by stimulating the immune system to enhance the body’s ability to destroy the tumor.
Mechanism of Action:
1. Direct Cancer Cells 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. This process destroys the cancer cell and can trigger an immune response, making the body more capable of recognizing and attacking the remaining cancer cells.
2. Innate Immune Response
The innate immune response is the body’s first defense against threats like viruses. Oncolytic viruses target and infect cancer cells, releasing signaling molecules such as cytokines, chemokines, and interferons. These molecules activate and guide the immune system, enhancing the immune response in and around the infected cancerous area.
Oncolytic viruses stimulate innate immune cells, including:
- Natural Killer (NK) Cells
These cells play a key role in the innate immune system by recognizing and attacking cancer cells. They are equipped with receptors that detect infected cells, including those expressing viral or tumor antigens. Through this mechanism, NK cells initiate an effective immune response against cancer cells.
- Dendritic cells (DC) and Macrophages
Oncolytic viruses help destroy cancer cells and release tumor-specific antigens. Antigen-presenting cells (APCs), like dendritic cells and macrophages, capture these antigens, process them, and present them to T-cells and B-cells. This activates the immune system, triggering both direct cancer cell destruction and a broader antitumor immune response.
3. Adaptive Immune Response
The Adaptive Immune Response is the body’s ability to create a targeted and long-lasting defense against cancer. It relies on specialized immune cells, including “memory T-cells,” which are trained to recognize and attack cancer cells based on past encounters. By activating these cells, the body can maintain ongoing surveillance to help prevent the recurrence of cancer.
How Does Oncolytic Virus Therapy Work?
Oncolytic viruses turn “cold” tumors into “hot” ones by transforming an immunosuppressive tumor environment into one that actively attracts and stimulates immune cells. This shift enhances the immune system’s ability to recognize and attack cancer cells, making tumors more responsive to immunotherapies. Oncolytic virus therapy offers hope for treating cancer that is resistant to traditional methods or when standard treatments are no longer effective.
Key Applications:
1. Residual tumors
After surgery, chemotherapy, or radiation therapy, when the tumor has been reduced to its minimal size, oncolytic viruses can effectively target and destroy the remaining cancer cells.
2. Resistant cancer
Malignant cells often develop resistance to conventional treatments. Oncolytic viruses bypass this resistance by directly targeting tumor cells.
3. High-risk recurrence cancer
In aggressive forms of cancer with a high likelihood of recurrence, oncolytic virus therapy lowers the risk of the disease returning by destroying even cancer stem cells.
Oncolytic Viruses in Cancer Therapy that We Use
IBDV (Infectious Bursal Disease Virus)
The use of IBDV offers several advantages for cancer patients. This virus selectively infects cancer cells, disrupting their metabolism and inducing apoptosis, without harming healthy tissues. IBDV effectively targets tumor cells, making it useful in the treatment of both localized and metastatic cancers.
NDV (Newcastle Disease Virus)
We currently use a Newcastle virus strain tested in 2017, which has shown the greatest effectiveness in destroying cancer cells compared to other viruses. Recent modifications of the virus have led to the development of a more potent strain with enhanced tumor detection capabilities.
How Can Oncolytic Virus Efficiency Be Boosted?
Oncolytic virus therapy is particularly effective when combined with immunotherapy, as it helps prepare the tumor microenvironment for a stronger response to these treatments. At Biotherapy International, after oncolytic virus therapy, we typically use immune checkpoint inhibitors or cytokine-mediated immunotherapy (CMI).
1. Checkpoint Inhibitors
Tumors that previously evaded the immune system (“cold” tumors) are transformed into “hot” tumors that attract immune cells. This boosts the effectiveness of PD-1/PD-L1 inhibitors, even in cases where these drugs alone show limited efficacy.
2. Cytokine-Based Immunotherapy (CMI)
The inflammatory response triggered by oncolytic viruses makes tumors more “visible” to the immune system. This increases the effectiveness of cytokine-based treatments such as Pegasys (pegylated interferon alpha-2a) and low-dose interleukin-2 (IL-2), helping the immune system identify and destroy cancer cells more effectively.
3. Oncolytic Viruses and Cancer Vaccines
Oncolytic viruses can also be combined with anti-cancer vaccines created from cryopreserved tumor tissue. For this reason, Biotherapy International advises its patients to cryopreserve tumor tissue removed during surgery.
The combination of oncolytic virus therapy and anticancer vaccines has proven to be highly effective and safe. This approach works through a dual mechanism: on one hand, it induces the destruction of cancer cells; on the other, it transforms non-immunogenic cancer cells into targets that can be recognized by the immune system.
Summary
Oncolytic virus therapy is a cancer treatment method where viruses target cancer cells without damaging healthy tissues. The viruses destroy the tumor and activate the immune system, enhancing the body’s fight against the disease. This approach is effective for treating cancers resistant to traditional methods and can improve the results of other immunotherapies. When combined with immunotherapy, the treatment strengthens the immune response against residual and recurrent tumors.
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