Viral therapy shows promise in ground-breaking clinical trial at The Ottawa Hospital Cancer Centre
May 20, 2010
A clinical trial conducted in Ottawa, Canada, and three U.S. cities has generated positive results that represent a major step forward in the development of oncolytic viruses for the treatment of cancer. Dr. John Bell and his colleagues at the Ottawa Hospital Research Institute (OHRI) have been developing oncolytic viruses for nearly a decade. Results presented today show for the first time that these viruses can be delivered safely in humans through direct injection into the bloodstream, resulting in selective targeting, replication and spread within tumour tissue. The study also reveals promising evidence of effectiveness at higher dose levels. The results were presented at the American Society of Gene and Cell Therapy Annual Meeting in Washington D.C. on May 20, 2010.
“We’re very excited because this is the first clinical trial to demonstrate that an oncolytic virus can selectively replicate inside tumours after intravenous delivery,” said Dr. Bell, a Senior Scientist at the OHRI and Professor of Medicine at the University of Ottawa. “Intravenous delivery is crucial for a cancer therapy because we want to be able to target cancer cells throughout the body, not just the large tumours that we can directly inject.”
The virus tested in this Phase I clinical trial is called JX-594. It is a member of the poxvirus family, derived from the vaccinia virus strain that has been used to vaccinate millions of people against smallpox. This virus has a natural ability to replicate preferentially in cancer cells, but it has also been genetically engineered to enhance this effect. Previous clinical trials have shown promising results when this virus is injected directly into tumours, but this is the first trial to examine intravenous delivery.
In the current clinical trial, 23 patients (including seven in Ottawa) were given a single intravenous infusion of the virus, at one of five dose levels. The patients had various types of solid tumours and had failed all other treatments. Six of eight evaluable patients in the higher dose cohorts exhibited disease control or response, while two of six evaluable patients in the lower dose cohorts exhibited disease control. Biopsies revealed selective replication of the virus inside tumours with destruction of tumour tissue in six patients who were treated at the higher dose levels. The most common side effects were flu-like symptoms.
“These are very encouraging results, especially for such an early stage trial,” said Dr. Bell. “We are now planning a number of other clinical trials, including a Phase III trial later this year, to further evaluate this therapy. At the same time, we are using our results from the clinic to make further improvements to these viruses in the laboratory. We think that this iterative cycle of laboratory research and clinical testing is crucial to the development of oncolytic viruses and other biological therapies for cancer.”
In recent months, Dr. Bell and his team have also made progress on a number of other fronts. They have published studies showing that certain oncolytic viruses can be combined together and combined with other therapies to synergistically target cancer in laboratory models. They have also perfected a procedure to manufacture highly concentrated and purified virus for clinical trials in a specialized facility at OHRI. OHRI is constructing a new Centre for Innovative Cancer Research to accelerate this research, with funding from the Canada Foundation for Innovation and The Ottawa Hospital Foundation.
The clinical trial was supported and administered by Jennerex Biotherapeutics (www.jennerex.com), a company co-founded by Dr. Bell in Ottawa and Dr. David Kirn in San Francisco, with support from many Ottawa and Toronto area investors. Dr. Bell was not directly involved in the trial, although his group, along with that of Dr. Harry Atkins, has conducted many of the supporting laboratory studies. Ottawa researchers involved in the trial include Drs. Laura Chow, Derek Jonker, Kelley Parato, Manijeh Daneshmand and Jean-Simon Diallo.
The Ottawa Hospital Research Institute (OHRI) is the research arm of The Ottawa Hospital and is an affiliated institute of the University of Ottawa, closely associated with the University’s Faculties of Medicine and Health Sciences. The OHRI includes more than 1,500 scientists, clinical investigators, graduate students, postdoctoral fellows and staff conducting research to improve the understanding, prevention, diagnosis and treatment of human disease. www.ohri.ca
Director, Communications and Public Relations
Ottawa Hospital Research Institute
613-798-5555 ext. 73325
Jennifer Cook Williams
Cook Williams Communications, Inc. (for Jennerex)