Oncolytic Viruses: A Primer

 

by Connie Son and Andrew Wight


 

Cancer accounts for more than one quarter of deaths in Canada. The current standard of care available to patients includes regimens of chemotherapy and radiotherapy. However, these treatments often cause severe side effects, as both are toxic, and kill tumours and healthy cells alike.

Oncolytic (“cancer-killing”) virus therapy provides a promising new take on cancer therapy by exploiting viruses that selectively target and kill tumour cells while leaving normal cells unharmed. We tend to think of viruses as harmful—after all, they infect and can kill human cells. Amazingly, however, some viruses are very selective in what cells they can infect—the picky eaters of the virus world—and the same mutations that turn a normal cell into cancer also make that cell delicious virus food. Researchers are now taking advantage of different viruses’ hunger for cancer to turn them into a treatment. So how does that work? Oncolytic viruses destroy cancer cells through three different potential mechanisms:

1) by directly infecting and killing cancer cells

2) by triggering anti-tumour immune responses and

3) by replicating in tumour blood vessels, cutting off the tumour’s supply of blood

Viral oncolysis was first observed in 1896, when doctors noticed the number of cancer cells in a leukemia patient decreased during an influenza infection. Around that time, a similar short-lived remission was recorded when a 4-year old leukemia patient got chickenpox. In 1949, the very first clinical trial of oncolytic virus gave infectious hepatitis B virus to 22 patients, putting 4 into remission. In the 1950s and 1960s, research into oncolytic viruses was vibrant and intensive: many human pathogenic viruses, including mumps virus, were tested as potential oncolytic agents. However, injection of impure viral preparations, such as infectious bodily fluids, often led to toxic side effects and even death. Since then, research into safer and better oncolytic viruses has led to significant advances in our understanding of oncolytic virotherapy.

Currently, many viruses with oncolytic properties are tested in clinical trials at the Ottawa Hospital Research Institute and around the world. Some oncolytic viruses, such as mumps and reovirus, are naturally selective for tumour cells. Others, such as measles and herpes simplex virus, are engineered to better target the tumour cells. This genetic engineering both reduces the danger and increases the effectiveness of these viruses, bringing us closer to realizing oncolytic virus therapy as a safer, more effective cancer treatment.

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