By Dr. Martin Smith
You know the feeling… It could start with a nagging headache. Or, it could be the flush feeling of an oncoming fever. Whatever it may be, many of us can relate to the symptoms of an impending viral infection. But, what if those same symptoms became signals of life saving treatments? For some patients in trials of a new cancer therapy, headaches and fevers represent markers of hope. Researchers have now engineered viruses to selectively recognize, infect and kill cancer cells in our body. These viruses, known as oncolytic viruses, are one of the next-generation cancer immunotherapies being studied to treat cancer.
Viruses can be deadly, and some have devastated the human race. However, others are being used for oncolytic virus therapy can actually be quite useful. When virions encounter a living organism something amazing happens. The virus particle will recognize and bind to signals on the surface of the host cell. Once bound, the virus enters the cell where it hijacks the internal cellular machinery to replicate – making more copies of itself. Unchecked, replication of the virus can cause the cell to explode . This releases the cell contents, including many new virus particles, which go on to repeat the infection cycle. This self-perpetuating behavior is common in the virus life cycle and is exactly what cancer researchers want to take advantage of when programming oncolytic viruses to preferentially target cancer cells.
Cancer cells function differently than healthy cells. Scientists have selected viruses that find cancer cells because of their altered function (1). Or, they have engineered special systems into the virus to recognize specific cancer markers. Oncolytic viruses happily bind and enter the host and replicate to produce numerous copies of themselves inside the cell. Gravid with new virus particles, the host cancer cell explodes, spewing out large numbers of cancer killing viral particles to continue the fight. The cancer cells release their insides during the explosion, activating the immune system to recognize and attack other cancer cells (2). This activation of the immune system is what leads to common symptoms of viral infection (an infographic illustrating oncolytic viruses can be found here).
It sounds perfect, right? Researchers across the world are definitely excited about oncolytic viruses. Early stage clinical trials are critical to determine the safety and efficacy (3). With safety being of utmost importance here, it is important to remember that viruses can be hard to control. Doctors will consider short-term side effects tolerable as long as they remain manageable. The long-term behaviour of viral therapies will also be important to understand. For example, some viral infections can actually lead to cancer. The human papilloma virus (HPV) has been shown to cause cervical cancer as well as head and neck cancer years after infection. There is no doubt that determining the effects of oncolytic viruses will be very important as the scientific community approaches drug development.
A cautious approach will be very important in using oncolytic viruses. The pros and cons associated with the use of these viruses forge a veritable double-edged sword. Perhaps it is time we pulled that sword from stone and used it in the fight against cancer.
This article was written by Dr. Martin Smith. Dr. Smith completed his PhD at the University of Waterloo studying how proteins can cause cancer. He currently works for the Ontario Brain Institute where he studies brain disease. To learn more about Dr. Smith and his research check out our members page.
(1) Ilkow et al., From Scourge to Cure: Tumour-Selective Viral Pathogenesis as a New Strategy against Cancer, PLOS Pathogens, 2014; 10(1); 1-8.
(2) Chiocca and Rabkin, Oncolytic Viruses and Their Application to Cancer Immunotherapy, Cancer Immunol. Res., 2014; 2(4); 295-300.
(3) Aghi and Martuza, Oncolytic viral therapies – the clinical experience, Oncogene, 2005; 24, 7802-7816.