Common cold to treat pancreatic cancer
The long-term survival rates from pancreatic cancer are notoriously grim. Steve Jobs, Patrick Swayze, Alan Rickman and Luciano Pavarotti are well-known recent victims. The prognosis tends to be so dismal because pancreatic tumours usually come to light only at very advanced stages of the disease, and by then the cancer has often also spread elsewhere in the body. Now Stella Man and Gunnel Hallden, from Queen Mary University of London, have found a way to modify a common cold virus to turn it into a form that can be injected safely into the bloodstream, where it selectively infects and destroys pancreatic cancer cells, including those that have spread to other parts of the body. Starting with Gunnel Hallden, Chris Smith heard how it works...
Gunnel - We have a long experience with developing cold viruses, so called adenovirus, into mutated versions of the virus that can only target and kill cancer cells. Our idea was based on targeting pancreatic cancers specifically; and another advantage with adenovirus - the cold virus - is that they can also sensitise cancer cells to the current chemotherapeutic drugs; so you would kill the cancer cell with the virus. You would also help the chemotherapeutic drugs to kill the cancer cells and then you could also re-activate the immune system, so that was the idea behind this.
Chris - So, Stella, what you were effectively trying to do here is to reprogramme what would be a cold virus and be spread by coughs and sneezes, and make it attack cancer cells. What was your approach to doing that? How did you do that?
Stella - In pancreatic cancer cells they have a protein displayed on the outside of these cells that is not displayed on normal cells. So we took advantage of that and we’ve changed the outer coat of the virus so that this virus can now target the cancer cell and not the normal cells. Another modification is that we’ve engineered the virus so that it can enter the normal cells but it won’t do anything. But when it enters into the cancer cell it can replicate and make more copies of itself, and then the virus bursts out of that cancer cell - killing the cell in the process and go on and infect the neighbouring cells.
Chris - So in essence, we have a virus that seeks our actively cancerous cells of the type that you're going for?
Stella - Yes.
Chris - It only grows actively in those cells and then once it’s grown and increased its number it buds out from the infected cells and infects all of the neighbouring cancerous cells if there are any so, in essence, what it’s doing is it’s growing until it runs out of cancer cells to kill and then it will just stop?
Stella - That’s right; that’s the idea behind it. Which is why we needed to also develop it so that it can be delivered via the bloodstream so that you can reach cancer cells that may have already spread away from its original site of growth.
Chris - And Gunnel, when you do this is it safe to inject this virus? Are you sure that it’s capable of targeting exclusively the cancer cells that you think it’s targeting or is it possible it could get into non-cancerous cells and do harm?
Gunnel - We haven’t obviously tried it in clinical trials yet but when we have done animal studies, and in animals it works exactly as Stella just explained. We can inject it in the blood, it will go to the tumour, it will express its genes and start replicating in the cancer cells, but we haven’t found it in any other tissues in the animals so it seems safe.
Chris- And Stella, one of the key things about cancer is it’s a moving target because it’s a genetically unstable entity and it means that it adapts, it evolves, and it becomes resistant to things like chemotherapy drugs. Is there a way in which the cancers could evolve to duck away from your virus so the virus can no longer attach itself to the cancer and get in via the mechanism that you’re relying on at the moment?
Stella - There’s always a possibility. I guess the length of the animal study is not long enough to see that but we didn’t see anything like that in our animal studies, so we haven’t seen any evidence of that.
Chris - It’s sounds very encouraging doesn’t it? Now given that these are cold viruses - adenoviruses - is there not a possibility that someone has experienced exposure to a virus like this before they could be immune to it and, therefore, that would limit its ability to work?
Gunnel - Yeah. It is possible, especially if you give the virus in the blood stream. But from other studies with similar viruses it seems to be possible for the virus to still reach the tumour the first time. Maybe the second time you would have to modify the virus a little bit but it’s not a major problem. Most of the viruses will reach the tumour.
Chris - What’s the next step them? You’ve proved that you can do this in cultured cells, you’ve proved you can do this in a limited way in animals. Animals don’t naturally get pancreatic cancers like we do so there is an inherent limitation to what you can achieve in animals, is the next step then to go into humans?
Gunnel - The next step would be we would like to first investigate a little bit more about the immune response in animals, and then we would go on and study toxicity in larger animals. After that, we would be ready to apply for funding to go into early stage clinical trials.
Chris - You probably get asked this a lot at dinner parties, both of you, but have you seen the film “I am Legend”?
Gunnel - Oh yes!
Stella - Yes!
Chris - Any reactions to that?
Stella - Those movies look very scary don’t they! It makes it look like a disaster zone so we were actually expecting questions like this but, luckily, this virus is not the same type of virus so it doesn’t carry the same risks!