The idea that a virus could help in killing cancer cells began in 1912, when an Italian gynecologist observed tumor regression in a cervical cancer patient after she received a rabies vaccination. It was in the late 1940s that physicians first intentionally injected viruses into cancer patients, but only a few positive results appeared. In the 1970s and 1980s, two groups reported shrinking of lymphomas (malignant cell infiltrations in the lymphatic system) after the patients’ exposal to measles virus. In the late 1990s, Frank McCormick and Daniel R. Henderson published separate reports showing that virotherapy could be targeted to human cancer cells. They used adenovirus, a virus causing the common cold, to eliminate human tumors that were grafted into mice. The modern concept of virotherapy was thus developed.
Some viruses like the one causing Newcastle disease naturally show a preference for certain types of tumor cells. However, other viruses like adenovirus must be genetically modified to target or to reproduce specifically within cancer cells. To insure that these engineered viruses target only the desired cells with no collateral damage, two main strategies have been developed.
First, transductional targeting involves the modification of the capsid proteins by attaching adapter molecules or by directly modifying them so that they will only fit to the receptors of tumor cells. For example, the scientists engineering oncolytic adenovirus are trying to find an adapter molecule to attach to its outer coat proteins and make its viral signal unfit for receptors on regular cells. Hence, this would cause the oncolytic adenovirus to only infect the tumor cells.
A second strategy, transcriptional targeting, involves placing a tumor-specific promoter with the DNA or RNA of the virus so that its genes will only replicate in cancerous cells. These viruses could thus enter normal cells but will remain dormant. If their hosts were cancerous however, the viral genes will be triggered to replicate and ultimately burst the targeted cells. Other strategies such as selective replication, uses the fact that the proteins restraining cell division (ex: Rb and p53) are inactivated in cancerous cells. This is how cancerous cells are able to divide repeatedly and frenziedly. We can thus engineer viruses so that they replicate only in cells where those proteins are inactivated (tumor cells).
Oncolytic virotherapy might be a better alternative to traditional cancer treatments such as chemotherapy and radiation since it would have fewer side effects. Moreover, virotherapy could also reduce the need for repeated treatments since oncolytic viruses can self-propagate and stay in the patient’s body until all the tumor cells are destroyed. Further, chemotherapy is much more effective if we consider that chemotherapy will kill as much as one healthy cell for six cancerous cells whereas, according to Robert L. Martuza, director of the Cell Genesys centre, viruses only one kill one healthy cell for 1,000 or more cancerous cells.
Virotherapy holds great promises as a novel treatment for cancer. Researchers, however, are unsure of the efficiency of these engineered viruses in the body. Methods to keep track of the virus’ efficiency are being developed. The imaging strategies for instance involve inserting a tracer such as a fluorescent protein on the virus.
The advantages of virotherapy include the ability to cause tumor destruction by numerous mechanisms. Nevertheless, this new technique may also present certain risks. Accordingly, to minimize risks, I think that the original virus should preferably cause only mild, well-known human symptoms such as the adenovirus. In addition, there should be some attempts in developing a secondary mechanism to prevent viral replication or to inactivate the virus. This will act as a back-up plan and minimize risks.
References
Curiel, David T. Nettelbeck, Dirk M. “Tumor-busting viruses”, Scientific American,
October 2003, pp.68-75.
McNaughton, Sean. “Viral attack”, Boston Globe.
McNaughton, Sean. Viral attack
