Tag Archives: Cancer

Fighting Fire with Fire: Using Poxviruses to Combat Cancer

Contributed by guest blogger: Brooke Schieffer ’12

In September of last year, a group of researchers infected cancer patients with a genetically engineered poxvirus. While this may sound like something out of a horror movie, it is actually quite the opposite: Breitbach et al. were performing a clinical trial to explore new, innovative ways to treat cancer tumors. Some people may be put off by the idea of having live viruses injected into their blood stream, but it’s actually not that uncommon. Indeed, many vaccines are actually live viruses. In fact, the vaccinia virus used in this clinical trial was derived from a vaccine for smallpox.

However, creating an attenuated virus to use as a vaccine and creating a virus that selectively infects and destroys cancer cells are two very different things. Before the scientists can create tumor-killing viruses, they first need to make sure that the virus can infect cancer cells while ignoring normal tissue cells in our body. To do this, they genetically engineered a poxvirus, called JX-594, that could replicate only in cells harboring activation of epidermal growth factor (EGFR)/Ras pathway (many epithelial cancers rely on this pathway). The virus, however, does not lyse the cell as this was only a trial to explore the possibilities of selectively cancer infection, not destruction.

The virus itself was chosen for several different reasons. Firstly, vaccinia (and, consequently, JX-594) is well adapted to intravenous transportation and displays some resistance to antibody neutralization in the blood stream. It can also spread quickly within tissues, making it ideal for infecting tumors (especially solid metastatic tumors). Finally, JX-594 replication is dependent on a commonly activated signaling pathway in epithelial cancers: the EGFR/Ras pathway. Furthermore, to determine if JX-594 was selectively infecting and replicating within cancer cells, the researchers incorporated the lacZ transgene (which encodes β-galactosidase) into the viral genome. They then could track β-galactosidase expression via immunohistochemical staining or tagged antibodies to see where the viruses were replicating in human tissue.

To test the effects of their virus, Breitbach et al. conducted a clinical trial with 23 cancer patients by intravenously injecting them with different concentrations of JX-594. They found their results to be quite promising: in the higher dose groups, they observed selective infection in tumor cells and expression of the β-galactosidase protein. And all with little apparent side effects—the worst of which were symptoms typical of a 24-hour flu. This is the first experiment in which an intravenously injected virus was able to selectively replicate in tumor cells and express a transgene. Of course, this is just the first step on the road to effective treatment. First off, this was only a preliminary study to determine if the virus could selectively infect cancer cells, they did not engineer the virus to kill the cells yet. As of now, it is simply a possible delivery method, not a way to kill cancer cells. But the researchers are hopeful that viruses such as JX-594 will eventually be customizable with proteins or siRNA to treat different types of cancer.

However, there are still many questions to keep in mind moving forward. Will we be able to insert a gene into these viral vectors that only destroys tumor cells? Can this delivery system be modified to infect cancers that do not use the EGFR/Ras pathway? What about the possibility of viral mutations that would allow the virus to infect healthy tissue? And what about the immune system’s role? How will multiple treatments work given the fact that the immune system will build up immunity against the virus because it is invading the body? Even with these questions, this clinical trial was still an innovative and interesting new approach to cancer treatment.


Brooke Schieffer is a senior at Vassar College, majoring in Drama.


Using Viruses to Battle Breast Cancer

Contributed by Guest Blogger: J. Warren ’14

Cancer is the second leading cause of death in the world today. This fact has made cancer research one of the leading studies in medicine, and any advancement in the field of cancer treatment is quite impactful. One of the more modern (and promising) approaches to treating cancer is through the use of viruses. An oncylitic virus is one that has been modified to infect cancer tissue in the body while not causing disease to the host. This should be possible due to the heightened susceptibility to viral infection of tumor cells, which have defects in certain antiviral response. The appeal of oncylitic viral infection is its ability to spread through the host, allowing it to attack any and all cancerous cells.
One highly attractive oncylitic virus is a mutant of vesicular stomatitis virus (VSV). A recent study investigated the effects of a mutant strain of VSV (rM51R-M) on breast cancer in both rats and humans. Though the virus was able to infect and kill the breast cancer cells without causing disease in the host mice, and could effectively destroy the tumors in vitro, unfortunately the research found that in vivo the viral infection is not sufficient for curing a host of breast cancer, and that VSV does not infect tumorigenic cells any more than normal cells.
Researchers grew several strains of human mammory epithelial cells with varying oncogenicity (chance to turn cancerous) and exposed them to varying multitudes of infection by rM51R-M. They observed that there was no significant difference in viral proliferation between the strains. They also looked at the effects of rM51R-M in mice with breast cancer, tracking the growth rate of the tumors according to the amount of infection.
Though the findings don’t amount to an effective way of defeating breast cancer, it does add valuable knowledge to the field. Future experiments can easily expand on these methods: using this data as a control, researchers could test other types of cancer, other oncylitic viruses, or perhaps the effects of compounding additional treatments. Perhaps this will also drive scientists to create completely new, engineered viruses that are able to infect only the tumor cells present and, some day, be able to completely eliminate multiple types of cancer.