Oncolytic viruses are viruses that have the capacity to attack cancer cells, rather than healthy ones. Although the possibility of viruses as a form of cancer therapy was first discovered in 1960, research on the use of oncolytic viruses for treatment of otherwise resistant cancer began much later. Nowadays, it seems to be a hot topic, but scientists are still trying to explore its full clinical potential.
Early Oncolytic Viruses
The link between viral infections and cancer regression focused on potentially dangerous agents such as poliovirus, adenovirus, and certain strains of herpes. However, some of these attempts proved hard to control, as they could result in a hard-to-treat systemic infection.
Because of this, the use of oncolytic viruses was abandoned for a time. However, towards the turn of the millennium, several breakthroughs in DNA and RNA mapping allowed researchers to focus on harmless viruses and if relevant introducing precise modifications to a virus’s DNA or RNA.
How do Oncolytic Viruses Work?
In order to know how oncolytic viruses can induce anti-cancer effects, it is important to understand that the anti-cancer effects of effective oncolytic viruses are mediated by two independent mechanisms of action. First, they produce direct anticancer cytotoxicity, and second, they produce an immune-mediated response using the patient’s immune response against cancer cells expressing viral antigens.
Oncolytic viruses are viruses capable of targeting specific types of cancer cells or to show a strong preference for them. These viruses have receptors that can attach themselves to cancer cells, and some of them are then able to enter the cell. Once inside, the viruses can begin replicating themselves. This results in the death of the host cell through a mechanism known as apoptosis. After being destroyed, the cell disintegrates and releases a large number of viral particles (known as “virions”) into the bloodstream or into neighbouring cancer cells. These virions will then attach themselves to other cancer cells nearby, and the process will be repeated.
This cycle is limited, however, as it is expected that a patient’s immune system would begin to notice the infection and attack the virus. If residual cancer cells remain at this point, the patient would need to be administered an additional dose of the virus. Perhaps this is why the anti-cancer effects of oncolytic viruses may be enhanced when administered alongside radiation therapy or chemotherapy: these partially suppress the immune system, and as such, delay the immune response against the viruses. The synergistic effects of radiation therapy, chemotherapy and oncolytic viruses may possibly allow oncolytic viruses to penetrate more easily through the cell wall of damaged cancer cells.
How Can the Efficiency of Oncolytic Viruses be Improved?
The expression of viral antigens on cancer cells that never activated the immune system can now serve as targets against “modified self” cells.In other words, turning “cold” targets into “hot” ones resulting in the induction of effective anti-cancer immunotherapy, the activation of the immune system against cancer cells “decorated” with viral antigens can be amplified by additional activation of the immune system.
One way to do this is by combining it with cell-mediated immunotherapy. In this case, the viruses are used to “flag” cancer cells, which can then be better targeted by the patient’s immune system. Alternatively, oncolytic viruses can be combined with cryopreserved tumor tissue and then used to produce anticancer vaccines. This is why Biotherapy International recommends its patients to cryopreserve some tumor tissue in its tumor bank, either after surgical removal of the tumor, or during a biopsy if the disease reoccurs. Sometimes, when residual or recurrent disease can be easily and safely accessed, oncolytic virus can be injected directly into the tumor tissue, turning an existing primary tumor or visible tumor metastasis into an in situ internal vaccine.
The combination of oncolytic viruses and anti-cancer vaccines has shown to be remarkably effective and user-friendly. This is because it works through a dual mechanism: on one side, it will induce cytotoxicity of cancer cells, and on the other one, it will turn non-immunogenic cancer cells into targets for the immune system.
How Are Oncolytic Viruses Administered?
Oncolytic viruses are usually administered via intravenous (IV) injection. As indicated earlier, for localized tumors in an accessible location, oncolytic viruses can also be injected directly inside the tumor mass. This will help turn the tumor site into an internal anti-cancer vaccine, that will continue producing the virions needed to fight cancer as well as serve as targets for continuous stimulation of the patient’s immune system against the cancer cells.
At Biotherapy International, we use two types of oncolytic viruses. These are derived from poultry viruses, to help ensure they will not target healthy human cells. The systemic IV administration of oncolytic viruses is still pending regulatory approval, but it can be done at one of our overseas satellite clinics.