The clinical study included 23 individuals whose cancer was advanced - it had spread to several organs in the body. The patients had not responded to standard treatments.
They were administered a single intravenous infusion of JX-594, a virus at five different levels of dosage. Ten days later biopsies were obtained and examined.
87% (7) of those who were given the two highest dosages had evidence in their tumor of viral replication, but not in surrounding healthy tissue. They also showed tumor-selective expression of a foreign gene - this gene was engineered into the virus to help the scientists identify it (the virus).
The patients tolerated the virus well at all dosage levels. The most common adverse events were flu like symptoms that cleared up within 24 hours.
Senior co-author, Dr. John Bell, a Senior Scientist at the Ottawa Hospital Research Institute, said:
"We are very excited because this is the first time in medical history that a viral therapy has been shown to consistently and selectively replicate in cancer tissue after intravenous infusion in humans. Intravenous delivery is crucial for cancer treatment because it allows us to target tumors throughout the body as opposed to just those that we can directly inject.
The study is also important because it shows that we can use this approach to selectively express foreign genes in tumours, opening the door to a whole new suite of targeted cancer therapies."
Dr. Bell and colleagues have been researching oncolytic viruses for over a decade. An oncolytic virus is one that attacks cancer cells. They developed KX-594 with Jennerex Inc., a biotherapeutics company founded by Dr. David Kirn, San Francisco, and Dr. Bell, Ottawa.
JX-594 originates from a vaccine virus strain that has been extensively used as a smallpox live vaccine. It can replicate naturally in cancer cells preferentially. JX-594 has also been genetically altered so that its cancer-fighting properties are more powerful.
Dr. Dell said:
"Oncolytic viruses are unique because they can attack tumors in multiple ways, they have very mild side effects compared to other treatments, and they can be easily customized for different kinds of cancer. We're still in the early stages of testing these viruses in patients, but I believe that someday, viruses and other biological therapies could truly transform our approach for treating cancer."
The trial evaluated tumor activity, even though its primary aim was to assess safety and delivery of JX-594. Three-quarters (6) of the participants on the two highest doses experienced either stabilization or shrinkage of their tumor, with this likelihood significantly dropping the lower the doses.
Dr. Dell said:
"These results are promising, especially for such an early-stage trial, with only one dose of therapy. But of course, we will need to do more trials to know if this virus can truly make a difference for patients. We are working hard to get these trials started, and at the same time, we are also working in the laboratory to advance our understanding of these viruses and figure out how best to use them. "