Viral cancer therapy shows early promise – experts respond

Scientists are cautiously optimistic about a trial cancer therapy which uses a virus to selectively kill tumor cells.

Canadian researchers have completed the first clinical trial in which viral therapy is delivered to cancer patients intravenously, and the virus selectively replicates only within tumour cells. The trial, published in Nature this week, show promising results.

Our friends at the Science Media Centre of Canada gathered the responses below from the study’s authors.

Feel free to use these quotes in your stories. To talk to a local expert on emerging cancer therapies, please contact the NZ SMC.

Dr. John Bell, co-author on the paper is Senior Scientist, Cancer Therapeutics, Ottawa Hospital Research Institute, Professor in departments of Medicine and Biochemistry, Microbiology and Immunology at the University of Ottawa and Chief Scientific Officer for Jennerex Inc.

How does the viral therapy work? How does it only infect cancer cells? 

“What we’ve discovered over the last 10 years in the lab, looking at the molecular biology of cancer, is that cancer cells have a predisposition to virus infection. If they become cancer cells, if they become immortal, they make a kind of a ‘deal with the devil’ and lose some of the antiviral machinery that normal cells have. The virus we used was selected because they can’t grow in normal tissues but they can in cancer cells.

“This particular virus is part of a vaccine – a vaccination that’s been used for the last 200 years, so we know it’s safe in humans. It’s then taken and engineered to be even more selective.

“What we discovered in tests is that it grows in solid tumours. Not in cancers like lymphoma or leukaemia. We believe it would be best for cancers like breast, head, neck, pancreas. ”

Have you noted any side effects – short-term or long-term?

“One of the things I’ve focused on in my career is targeting treatments. Chemotherapy, as you know, is associated with many side effects. The more targeted to the tissue a treatment is, it should have very few side effects, and in the patients that we studied we never saw any side effects. Just flu-like symptoms for 24 hours or so, and then nothing. Whether the virus would promote metastatic growth in any way, we don’t know yet, but we did find that the patients with the highest dose had the fewest metastasis. This trial is closed, which is why we were able to publish, but we’ll follow the patients”

Why is it important to be able to deliver the drug intravenously?

“One reason is that in the clinic, people like to give treatment intravenously – clinics are set up for it, and they understand it. We want any treatment to fit into the system that’s already in place.

“The second thing is that, in cancer, the real challenge is not the solitary tumour that can be identified and excised but cancer that has spread or metastasized to other parts of the patient’s body. . The best way to get to metastatic disease is through the bloodstream. Then it circulates in the blood, and can attack the metastatic cells wherever it finds them.

“Chemo does circulate in the blood, but it doesn’t always affect these cells the way we’d like because it attacks non-cancer cells as well. If you want to get a drug everywhere, you have to saturate the body with it, so it reaches all tissues. But with viral therapy, it just takes one virus to attack a cancer cell and it will be able to replicate and spread locally within the tumour. ”

What sort of drug or transgene product will it be able to deliver? 

“There’s three aspects; there could be a gene that would accumulate a certain isotope so we could see all tumours with a PET scan. The second way is with a gene that will turn a non-toxic drug into a toxic drug so the effect is very local. The third way is if the transgene actually is a toxin. ”

What’s the timeline for this? 

“It’s a tough call – we have to have definitive data before the FDA and other agencies will allow it on the market. We are launching a Phase II trial, that will last about 18 to 24 months. We’re also looking at starting a Phase III trial next year that would take about 2 years to complete. Hopefully, after that we will have enough data. ”

Will this accelerate development in this area by other researchers? 

“I really hope it does. A lot of scientists are smarter than me, and if we can get them on the bandwagon I think we’ll see this field realty take off…it’s still a clearly undeveloped area. we needed a study, like the one we’ve just published. There’s been a lot of skepticism in the field – but it’s an emerging technology.

“This study is an international effort – we’ve got people from Korea, the States. It’s really a team effort that let us do this.

“It is not clear yet from our trials how many doses we will be able to give intravenously before the immune system would block further delivery. The virus we are using however has multiple forms and one of the particles it makes during its life cycle has a cloaking mechanism that may allow it escape neutralization by the immune system. In the Nature study all patients had been previously immunized as children and one patient still had a significant antibody response yet we still saw virus delivery. More studies are needed to more fully test this issue however. ”

How the Study is Funded?

“Bell’s work is supported by the Terry Fox Foundation, the Ontario Institute for Cancer Research, the Canadian Institute for Health Research, Local Ottawa Foundations. In addition Jennerex Biotherapeutics is supported by investors from Toronto, Ottawa, the US and Korea and in partnership with Transgenes Inc in France, Green Cross in Korea and Lees Pharmaceutical in China. ”


Dr. John Hiscott, Professor of Medicine,Microbiology & Oncology,McGill University, Principal Investigator, Vaccine & Gene Therapy Institute of Florida

How does viral therapy offer an edge over chemotherapy?

“This a very important paper describing a new oncolytic virus vector that can target and kill cancer cells in patients, and the study demonstrates clinical benefit without serious side effects. This group has other impressive studies that are also underway.

“This area of research is generally referred to as oncolytic virotherapy, and represents a completely different approach to cancer therapy compared to traditional chemotherapy. The issue with chemotherapy has always been that it is very toxic; for every 10 cancer cells chemotherapy kills, chemo kills one normal cell. That’s a poor therapeutic index. Oncolytic viral therapy on the other hand can kill 1,000-10,000 cancer cells for every normal cell, thus offering the possibility of reduced side effects. This particular vector is a virus originally used in immunization against smallpox and has already been administered to millions of people, thus making it a safe therapy and making it easier to pass through regulatory safety hurdles.”

Is anyone else worldwide doing this, or close to doing this? How significant is this paper from that perspective?

“This area of experimental cancer therapy has been a small but rapidly expanding area of research. At least half a dozen biotech companies are conducting clinical trials with oncolytic vaccine approaches and recently, a large pharmaceutical company – Amgen became involved, through their purchase of one of these biotech companies Biovex. This purchase represented the first large infusion of financial resources into this area. Otherwise, this research has been funded by organizations such as the Terry Fox Foundation, the Canadian Cancer Society in Canada and the National Cancer Institute in the United States.

“The Canadian Cancer Society and the Terry Fox Foundation in Canada have been very supportive of this research, and several leading discoveries have come from this country. This is an important flagship area of cancer research for the country.  In terms of overall significance, this study demonstrates the efficacy of a novel oncolytic virus, with studies moving rapidly into phase II and III clinical trials. ”

What potential side effects – short or long term – might this approach have?

“It’s rather amazing – we often talk about viruses and think of horrible diseases, but the viruses used in oncolytic therapy have proven to be relatively harmless in clinical trials. In the present case, JX-594 is modified version of a vaccine strain, in other cases, the virus used does not cause disease in humans. These viruses can search out and kill cancer cells, while leaving normal tissues intact. Relatively few side effects are reported – usually flu-like symptoms for 24 hours, as a consequence of the treatment with virus.”

What hurdles does viral therapy still have to overcome? (i.e., the body’s immune system attacking the virus before it can have an effect on the cancer cell?) What specific hurdles has this paper overcome that move it forward? 

“There are several types of hurdles to virotherapy. One type of hurdle is biological: most viruses targeting tumors will replicate for a defined period of time and then stop replicating because the immune system mounts a response. One of the next scientific challenges will be to develop effective ways to get the body’s immune system to attack the cancer cells as well. This is an area that needs to be explored further.

“There are two other hurdles – one relates to safety regulations. This is a biological therapy, as opposed to a small molecule drug where delivery, dose and endpoints can be monitored closely; thus regulatory agencies have been very cautious before allowing these trials to proceed. However it is important to recognize that many patients have reached the end of conventional cancer treatment and would be ready to try new experimental cancer therapies.  The final hurdle is the pragmatic one of finances; this type of research requires a lot of money, and it is important for government funding agencies and pharmaceutical companies to support these kinds of programs. ”

How do viruses target cancer cells and not normal cells? 

“Most normal cells, when they encounter a virus will produce high levels of molecules like cytokines and interferons that limit virus multiplication/growth. The fact that you generate an antiviral response limits virus growth and ultimately allows the tissue to recover.

“In cancer cells, pathways controlling the antiviral immune responses are often defective or mutated, thus virus grows preferentially in the cancer cells. Also, in cancer cells, cell growth pathways are always turned on – in the case of viruses like JX-594, the Ras pathway is activated and this also helps virus to grow. As an example, if you infect normal cells of the body with virus and also infect the same type of cancerous cells, you will get some virus growth in the normal tissue, but you will get between ten thousand and a hundred thousand times more virus from the tumour cells. ”

How do you overcome the body’s immune response attacking the virus vector before it can in turn attack the cancer?

“It comes down to an issue of dosage. By using a high dose of vaccinia virus, you overcome the immune response, at least temporarily. The amount of antibody in circulation as a result of vaccination is sufficient to prevent symptoms but is not sufficient to prevent infection itself. On one hand, with an oncolytic virus approach, a large amount of virus is delivered to target the tumor, while on the other hand, the high dose of virus is also sufficient to overcome the limiting amount of circulating antibody against that virus. As for suppressing the immune response at the same time, you don’t want to do that, you want the immune response to work in concert with the virus to target and kill the tumor cells. ”