Triggering the immune system to attack tumours

Current cancer therapies often involve using drugs that are toxic to rapidly growing cells and this inevitably means that some healthy tissues get hit too. But if we could trigger...
04 November 2012

Interview with 

Dr David Kirn, Jennerex Biotherapeutics, San Francisco


Current cancer therapies often involve using drugs that are toxic to rapidly growing cells and this inevitably means that some healthy tissues get hit also which causes side effects like hair loss, rashes, and organ damage.  But if we could trigger our own immune system to target a tumour, then we'd have a way to selectively combat the disease while simultaneously minimising the harm to other tissues.  Chris Smith heard from David Kirn, Chief Medical Officer of the San Francisco based company Jennerex Biotherapeutics, how they're using modified viruses to attack cancers... 

David K. -   What we do is we get the body's own defence mechanism, the immune system, to turn its sights on cancer cells in the body and destroy them.  The way we do that is we engineer a virus that we call JX-594 to specifically target cancer cells, multiply in them and burst them, and at the same time produce many very potent danger signals to the immune response to get the body's immune system to turn on the cancer.

Chris -   So effectively, by making the virus infect the tumour and break open the tumour cells, because the immune system is seeing a virus infection and cancer cells, it doesn't only combat the virus infection.  It also combats the cancer.

David K. -   That's exactly right and then we have one other little trick that we use in JX-594 and that is to insert the gene for a very immune stimulatory protein into the virus, so virus-infected cancer cells will express this very potent cytokine that stimulates the immune system to recruit immune cells into the tumour to kill the tumour cell.  That cytokine is called GM-CSF and it's something that our body makes at low levels all the time, but now, with the JX-594 infection of cancers, they now express very high levels of GM-CSF, right in the tumour itself  to recruit the body's immune system into the tumour and activate it.

Chris -   So, when you apply the virus, do you inject it into one part of the tumour somewhere and then let it multiply?

David K. -   Well, it's an interesting thing about using virus therapy.  We can administer the product several different ways to cancer, so we can give it directly into the tumour, and one of the advantages of JX-594 which is a type of virus that is very stable in the blood, we can also give it IV.  So just through IV infusion into the arm as you might get a normal antibiotic and it's able to seek out tumours throughout the body and infect them, and lyse them.  So that's one of the interesting things about this approach.  We can use multiple methods of administration.

Chris -   What is the virus that you're using to do this?  I know you've given it obviously a research name because it's now modified organism, but what did it start out life as?

David K. -   Well, it started out as what's called a vaccinia virus.  So vaccinia virus is something that's very, very familiar to the medical community and to almost all of your listeners who are over the age of 40.  So, this is a virus that was used as a vaccine in children to eradicate small pox.  So it's not a small pox virus, but it tricks the body into protecting itself against small pox.  This is a virus that came from cow pox which was discovered by Edward Jenner in England over 200 years ago and led to the use of live viruses to vaccinate people against infectious diseases.  So, hundreds of millions of children throughout the world received live vaccinia virus as a childhood vaccine and that led to the eradication of small pox which is arguably one of mankind's greatest successes.

Chris -   The problem is, if people have had that small pox vaccination, does this not mean they will now be immune to vaccinia which means that if you come along and try and treat them when they've got a cancer with your therapy, it's not going to work.

David K. -   Yeah, that was a very important concern that we had.  We thought vaccinia was the ideal virus for this approach, but we were worried about that, so what we've done is studied in clinical trials whether pre-existing immunity to the vaccinia would prevent the effectiveness of the product.  Fortunately, because we use such high doses and the virus replicates to such high titres - high amounts in the tumour, we get very nice efficacy regardless of whether someone was vaccinated in the past as a child.

Chris -   One of the really attractive aspects of this is if you initiate the immune response in one part of the tumour then whether there are just single tumours or other tumours and metastases elsewhere in the body, they're going to get hit subsequently too by the immune response, but is this safe?

David K. -   Well, I think we had reason to believe it would be safe because the virus is very, very specific for cancers.  It only gets turned on in cancer cells that have these very common cancer pathways turned on and those are not turned on in normal cells.  So we don't see activation and multiplication of the virus in normal cells.  And then the body's immune system is very, very clever at determining foreign cells versus normal cells.  And so, we believed it was going to be safe and we've now treated roughly 200 patients with this therapy, and we've seen that to-date, it's been very, very safe.  We've not seen normal tissue damage or any sort of autoimmune problems with this therapy.

Chris -   I'm glad you brought up the issue of trials because what are those trials showing?  What sorts of cancers have you been able to treat with this and what are the outcomes?

David K. -   Well, as I said, we've treated about 200 patients to-date in phase 1 and phase 2 clinical trials, and we've treated a wide range of solid tumours including colon cancer, liver cancer, kidney, ovarian, melanoma, and others.  And what we've seen, as the virus does become activated in the cancer, it multiplies, it expresses this immune stimulatory cytokine called GM-CSF.  So it appears to be working in the way we thought it would in cancers and we've looked for effects on normal tissues and we've not seen those any safety issues with normal tissues, so it seems to be very, very cancer selective.  And then finally, most excitingly we've seen significant tumour destruction, tumour shrinkage in a number of patients and we do have randomised clinical trial data showing that at a high dose JX-594 actually improves the survival duration of patients with very advanced liver cancer.  So it's a very exciting time.  We're now moving into later stage, larger clinical trials that will be randomised to try to get the parts approved and on the market.


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