Importance of Oncolytic Viruses

The word Oncolytic is derived from two words, “onco” which means cancer and “lytic” meaning killing. So, oncolytic viruses represents an innovative potential cancer therapy known as virotherapy that seeks to harness the natural properties of viruses to aid in the fight against cancer. In other words, oncolytic viruses are human viruses that infect and replicate in cancer cells, destroying these harmful cells and leaving normal cells largely unaffected.

Clinical data suggest that oncolytic viruses may offer therapeutic advantages over existing cancer therapies such as chemotherapy and radiation. The three primary benefits identified to date include the following:

High Therapeutic Index: Compared with traditional therapies, oncolytic viruses have been shown to have a high therapeutic index. In some instances, the therapeutic index of oncolytic viruses has been found to be as high as 100,000 to one. In other words, for every 100,000 tumor cells that are killed, only one normal cell is killed. This is significantly higher than the therapeutic index commonly seen with chemotherapy (six to one) and may result in greater efficacy with fewer side effects.

Better Anti-tumour Efficacy due to Viral Replication: Unlike some traditional therapies that are cleared from the body within a specific amount of time like chemotherapy, oncolytic viruses are engineered to proliferate and remain in the body until all of the cancer cells are destroyed. This self-proliferation could potentially mitigate the need for extensive re-treatment and result in greater efficacy and patient convenience.

Synergistic Anti-tumour Activity with Other Cancer Therapies: Some oncolytic viruses have been shown to have significant synergy with conventional cancer treatments such as radiation and chemotherapy. This type of combination therapy could potentially lead to greater therapeutic efficacy.

Research is currently being conducted by institutions around the world using both non-engineered and engineered viruses to evaluate their use in the fight against multiple types of cancer. Non-engineered viruses are naturally occurring viruses that innately preferentially target and replicate in certain types of tumor cells. Some non-engineered viruses include the Newcastle Disease Virus, Autonomous Parvovirus, and the Reovirus. Conversely, engineered viruses do not innately selectively target and replicate in cancer cells. Scientists must genetically modify the virus to selectively target and/or replicate within specific types of cancer cells.

Today, there are three main approaches that are being explored in the development of engineered tumour-specific oncolytic viruses. Although the three approaches differ from one another, they all share a common goal, the destruction of cancer cells as a result of viral replication. The three approaches are as follows:

Selective Targeting-Capsid Protein Modification: The capsid protein, the external surface of the virus, is modified so that the virus would specifically target cancer cells, completely avoiding normal cells. The virus would then replicate within the targeted cancer cell, ultimately leading to cell death.

Selective Replication in the Absence of an Anti-tumour Gene: The virus is genetically modified so that it will replicate only in the absence of a gene believed to inhibit tumor cell growth, such as P53. While the virus “passes through” normal cells, it is triggered to replicate in cancer cells that do not exhibit an anti-tumour gene, ultimately leading to cancer cell death.

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