Obtaining a virus is no easy feat, but for many scientists across the country, viruses are making the future of cancer treatment appear very bright.
“Viruses are so efficient,” says Dr. Robert Kratzke, a professor of Hematology, Oncology, and Transplantation at the University of Minnesota. “You can put a ratio, like 1-to-1, virus-to-cells in a petri dish, and every single cell is hit with a virus.” It is this efficiency which has helped the oncolytic virus therapy movement grow significantly during the last two decades.
Not all viruses are created equal, but some, called oncolytic viruses, can infect and kill tumors. According to the National Cancer Institute, some oncolytic viruses work in part by “triggering an immune response in the body against cancer.” Oncolytic viruses infect a tumor cell and make copies of itself until the tumor cell ruptures. The ruptured cell then releases materials, like tumor antigens, which allows the immune system to recognize the cancer. “We all know from our own practical experience that viruses are brutally efficient at translating colds and diseases and the like, so the superb efficiency at infecting cells was very attractive,” says Kratzke.
Today, viruses are firmly established as a potential option to enhance and mediate immunotherapy.
Although oncolytic virus therapy treatment appears to be an innovation of the current century, its study is nothing new. Since the late-1800s, doctors have recognized cancer remission in some patients after receiving a viral infection. “Early case reports emphasized regression of cancers during naturally acquired virus infections, providing the basis for clinical trials where body fluids containing human or animal viruses were used to transmit infections to cancer patients,” says Elizabeth Kelly and Stephen J. Russell of the Mayo Clinic College of Medicine in a report for the journal Molecular Therapy. “Most often the viruses were arrested by the host immune system and failed to impact tumor growth, but sometimes, in immunosuppressed patients, infection persisted, and tumors regressed.”
It was not until the 1990s, with advancements in genetic-engineering technology, that the science of oncolytic virus therapy progressed. Dr. Matthias Gromeier of the Duke Cancer Institute told the National Cancer Institute another shift occurred around 2005 with the advancement of immunotherapy. “Today, viruses are firmly established as a potential option to enhance and mediate immunotherapy,” Gromeier says. As of 2019, only one oncolytic virus (a genetically modified form of the herpes virus) has received approval from the Food and Drug Administration for the treatment of melanoma.
While acquiring FDA approval may be slow, many researchers across the country are still initiating or seeking funding for their clinical trials for oncolytic virus therapy. Kratzke has partnered with Dr. Russell at the Mayo Clinic on a study examining a weakened strain of the measles virus against multiple myeloma, a cancer of the blood.
Russell believed mesothelioma, which is an area of expertise for Kratzke, would be an ideal cancer to test as well during the multiple myeloma study, because the measles virus can be injected into the pleural space of one’s body. “The measles virus can get in, and it infects […] the mesothelioma cells and kills them,” says Kratzke. “And it can replicate in the host, in the patient, or the lab animal, and spread […] to other places or throughout the body and kill cancer cells there.”
Another virus—vesicular stomatitis virus (VSV)—has also shown promising results for Kratzke and his team. According to Kratzke, “[VSV] can infect humans, but people don’t get sick from it, and most of us have not been exposed to it.” Unlike other viruses, the lack of major side effects with VSV is particularly enticing for researchers. “We’ve had to overcome some of the reflexive fear about using a virus and possible disease that the virus could cause,” he says.
After using an oncolytic virus for treatment, doctors expect to administer immunotherapy drugs like Opdivo or Keytruda because of the immune response generated by the virus killing the cancer cells. “A lot of cancer-related proteins are exposed to the bloodstream, and so the body can now mount an immune response to that, and the Opdivo or Keytruda accentuates that reaction,” says Kratzke.
However, receiving separate funding for a trial specifically geared toward mesothelioma has not been easy. “I think we need to demonstrate in mesothelioma patients who have already had conventional chemotherapy, which […] doesn’t work that well, that [viral therapy] works, and that’s just the next step,” Kratzke says. All of the necessary steps to acquire funding for a trial—from understanding the doses, to safely acquiring the virus, to obtaining the clinical data—is all in place. Kratzke has applied for funding, but whether that funding will come through for him and his team remains to be seen.
In the meantime, Kratzke and many others continue to advocate for oncolytic virus therapy as the future of cancer treatment. Soon, the idea of receiving viruses to treat cancer won’t seem so worrisome to non-researchers. “I might be wrong, but maybe in five or 10 years, the virus therapy shelf in the oncology pharmacy in the clinic will be there,” Kratzke offers. “They’ll just say, ‘OK, this is where we keep our chemo drugs, this is where we keep our immunotherapy drugs, and this is where we keep our viruses.’”