A Virus Can Treat Cancer?

A chicken-killing virus? To treat cancer?

Ever thought a chicken-killing virus could be used to treat cancer? Probably not. But a recent study has discovered amazing potential in using Newcastle disease virus to kill prostate cancer cells. In what is known as oncolytic virotherapy, viruses like the one used in this recent study are implemented as tools to destroy cancer. Newcastle disease virus (NDV) is an avian paramyxovirus that infects wild and domestic bird species. It can cause flu-like symptoms and mild conjunctivitis in humans, but does not pose a significant threat to us. In addition to NDV being essentially non-pathogenic to humans, it can be used in cancer treatment strategies because it is an inherently tumor selective oncolytic virus. This potentially daunting description essentially translates to NDV’s ability to target and destroy cancer cells without posing a threat to healthy cells. In the recent study by Shobana et al. (2013), the authors investigated this virus’s potential for specifically killing human prostate cancer cells.

Newcastle disease virus

Why is this treatment so important?

Such an investigation has significant clinical implications, given that prostate cancer is the second leading cause of cancer-related deaths in the United States. To put things in perspective, almost 17% of men will develop prostate cancer at some point in their lives. Treatment of prostate cancer typically involves hormone therapy or chemotherapy, both of which have significant adverse side effects. Furthermore, current treatments for hormone-resistant prostate cancer only marginally increase survival and are often aimed at palliative, or pain management, care. Given the adverse effects and low effectiveness of the typical treatment approaches, there is much hope that we can begin to turn to oncolytic virotherapy as a novel approach to prostate cancer treatment. Using NDV as the vector in this therapy would alleviate patients from the often painful side effects of more standard cancer treatments. Although many issues are still associated with oncolytic virotherapy,  Shobana et al. (2013) present findings that make scientists hopeful such a treatment will soon have real clinical applications for treatment of what is now the second leading cause of cancer death in men.

How did they modify the virus to use it for cancer treatment?

            You may be wondering how a seemingly harmful virus can be used to deliver treatment. Wouldn’t the negative effects of the virus itself negate its positive oncolytic capabilities? Thankfully scientists have already developed strategies to mediate this potentially problematic association. Not only is NDV essentially non-pathogenic for humans, but it can also be modified in such a way so as to ensure that it only its oncolytic effects are at work when it infected patient cells. Shobana et al. (2013) were able to perform such a modification by altering the virus so that it is only capable of replication when in the presence of an active prostate-specific antigen. This antigen is a specific substance on the prostate cells that is recognized by the patient’s immune system. In the case of this study, the authors altered a protein on the NDV (called the F protein) so that it could only be cleaved, or cut, by the prostate-specific antigen. This cleavage event is needed for NDV to replicate. The virus therefore targets prostate cancer cells with this prostate-specific antigen. The authors were essentially able to engineer a highly specific virus that efficiently and specifically replicates in prostate cancer cells.

How well did it work?

Their modification of the virus ensured that it would specifically target prostate cancer cells, but the next question they needed to answer was how well this targeting could translate into efficacy for oncolytic virotherapy. In other words, can the modified virus really kill cancer cells? In order to answer this question, they performed experiments using the NDV in a tumor model. This model mimics prostate cancer in a real human host but is done in the control of a laboratory. What they found was pretty exciting. The virus did in fact kill prostate cancer cells! Furthermore, because they engineered it to have high specificity for cancerous cells, it did not harm normal human cells. The results from this study show that, at least in the laboratory model, the modified NDV seems to have effective oncolytic capabilities. Also, past studies that have used an unmodified or natural version of this virus as a treatment tool have had to use very large doses to see effects. Yet with the modification done in this study, the authors believe that their specific strain of NDV can be effective at destroying prostate cancer at much lower doses.

What does all this mean?

The modification of NDV’s F protein yields a newly engineered viral strain has the potential to be safer and even more effective at lower doses. Ideally, this virus could be injected into a prostate cancer patient, either into the bloodstream or directly into a prostate tumor, and the NDV could find and destroy cancerous cells. Does this method seem a little too good to be true? That may be the case, at least at this point in time. Shobana et al. (2013) performed their experiments in a tumor model in the lab, rather than in an actual human patient. As you might expect, the human body is much more complicated than a fully controlled experimental tumor model. Before this specific form of oncolytic virotherapy can be used as a viable treatment method, more trials need to be performed to assess the efficacy of the modified NDV in an actual human or animal host. Nevertheless, if this method is in fact successful in clinical trials in the future, we may find ourselves thanking a chicken-killing virus for countless lives saving lives. Who would have thought?

References

Primary article:

Shobana R, Samal SK, and Elankumaran S. 2013. Prostate-specific antigen-retargeted

recombinant Newcastle disease virus for prostate cancer virotherapy. Journal of Virology 87(7): 3792-800.

Secondary articles:

Newcastle disease virus. (2013, February 20). Retrieved from

http://www.cancer.gov/cancertopics/pdq/cam/NDV/patient/page1

Prostate Cancer Overview. (2013, January 17). Retrieved from

http://www.cancer.org/cancer/prostatecancer/overviewguide/prostate-cancer-overview-key-statistics

Russell SJ, Peng KW, and Bell JC. 2012. Oncolytic virotherapy. Nature Biotechnology

30: 658-670.

Virginia Tech study finds virus promising for cancer treatment. (2013, April 8).

Retrieved from http://www.vtnews.vt.edu/articles/2013/04/040813-vetmed-prostatecancer.html