by Tom Bulford
Posted 9th March 2016
When former US President Jimmy Carter learnt last August that he had cancer in his brain, he said that he was ‘perfectly at ease with whatever comes.’
I guess at the age of 91 fatalism is a pretty good philosophy but Carter could have afforded a dash of optimism as well.
He was given Merck’s Keytruda, one of the new generation of cancer immunotherapy drugs, and three months later his cancer had gone.
How does Keytruda work?
Think of it this way. Suppose a tall guy with long arms is attacked by a short guy with short arms. If the tall guy grabs his opponent by the neck the latter can swing his fists as much as he likes but he will never land a blow.
Now think of the tall guy as a cancer cell and his attacker as a killer T-cell of the immune system. The cancer cell is able to hold the T-cell at bay.
Keytruda works by blocking the tall guy’s move. His hands are prevented from holding his foe at arms’ length, allowing the short guy to move in for the kill.
Because it works by interfering with this cellular interaction, Keytruda is one of a new class of cancer drugs known as ‘checkpoint inhibitors.’
Nobody knows more about cancer immunotherapy than Lindy Durrant, a professor at Nottingham University but also a founder and joint CEO of one of the UK’s great hopes in this field, Scancell.
I have been up to Nottingham to meet her and her fellow CEO Richard Goodfellow, and my tall guy/short guy analogy is inspired by her depiction of a constant battler raging between our immune cells and cancer cells.
Your immune system conducts full-time surveillance of your body, sending out the killer T-cells to destroy anything it does not like the look of.
Cancer cells are good at evading this surveillance system probably because, although they have gone astray, they were originally just normal human cells.
But as they get older, dividing and multiplying and picking up more genetic mutations in the process, they do more than just run and hide from the immune system. They turn and fight. They become aggressive.
In this process, called subversion, the cancer cells counter-attack the T-cells. And it is at this point, perhaps fifteen years after the first cancerous cell has appeared in the body, when the disease really goes into overdrive and spreads rapidly.
We do not usually recognise that we have cancer until it has reached this late, aggressive stage – and this is a problem. Precisely because it is well established we need to throw some very powerful drugs at it.
Previous generations of cancer drugs have been highly toxic, killing cancer cells and healthy cells indiscriminately.
Checkpoint inhibitors are an improvement because they target cancer cells and they have demonstrated good results. Keytruda, Yervoy and Opdivo are the three leaders at present but several others (including Roche’s Atezolizumab) are heading for the market.
For some patients they have worked remarkably well. They are also easy to administer, unlike another modern approach, cell therapy, where cells must be taken out of the body, genetically engineered and then replaced.
But checkpoint inhibitors are far from perfect.
While a minority of fortunate patients find that their cancer disappears the majority are not cured and by unshackling the immune system, which is a very powerful force, these drugs can also cause plenty of collateral damage.
Keytruda has had a remarkable impact on Jimmy Carter and on others with melanoma or lung cancer who are now in remission.
But the former US President might not be quite so serene if he reads the list of Keytruda’s side effects, which include inflammation of the lungs and colon, hepatitis, kidney failure and perforation of the bowel – and these can be fatal.
So, Professor Durrant explained, we need to do two things.
We need to provide some assistance to these late stage cancer drugs, but even more usefully we need to tackle cancer early on, before it has become aggressive.
Unwittingly carrying cancer
Many of us will harbour cancer cells without realising it. Indeed we may well die before it ever becomes a problem.
The average age at which cancer is diagnosed is roughly 70, meaning that the first cancerous cells would have appeared around the age of 50.
Ideally then, for the sake of our health but also to save some of the huge costs associated with late stage treatment, we would like to tame cancer before it gets subversive and aggressive.
The way to do this is with a vaccine.
In their early days, before they have developed too many mutations and turned aggressive, cancer cells will provoke an immune reaction and can be tamed by the body’s natural defences.
We do not want to be bombarding the body with toxic drugs at this stage because they would do more harm than good. We just need to educate the immune system to recognise the cancer cells and this is precisely what a vaccine does.
By introducing a small amount of the enemy into the body it alerts the immune system and programmes it to recognise any recurrence.
Already we vaccinate against the human papilloma virus, which can cause cancer. However while cancer can be the consequence of a virus it is usually the result of DNA mutations.
For this we do not want vaccines that are designed to prevent disease in the first place, but those that will help the immune system to attack a disease that already mildly exists.
Scancell’s answer is a powerful vaccine called SCIB1.
In a study of 28 patients with metastatic melanoma (i.e. skin cancer that has spread elsewhere) SCIB1 has achieved remarkable results with some now in their fourth year of remission.
It is based on Scancell’s ImmunoBody® platform and this could be used to develop vaccines against other types of cancer as well as chronic infectious diseases.
Vaccines are cheap, easy to manufacture and they are non-toxic. So they could offer a real breakthrough in cancer treatment, especially if modern diagnostic tests can spot cancer early and allow the vaccines to do their work before the disease has become aggressive.
But Professor Durrant also believes that vaccines can play a part in late stage cancers if administered alongside checkpoint inhibitors. While the latter would free the immune system to tackle the cancer cells Scancell’s vaccine would boost the former’s strength.
Scancell: lots of promise, lots of risk
Trials on mice have supported this theory and Scancell intends to commence a human study in the USA next year.
Aside from the health benefit there is an economic necessity to improve outcomes. While checkpoint inhibitors have created justifiable excitement they are prodigiously expensive.
A course of Keytruda costs about $150,000 per year. But since it only helps about 30% of patients the cost per success is an eye watering $500,000 and no public health service can afford to spend that amount of money on every cancer patient.
By increasing the success rate Scancell’s vaccine would effectively lower the cost.
As well as the trial of SCIB1 in conjunction with a checkpoint inhibitor Scancell would also like to run a full scale Phase III trial for metastatic melanoma.
And it has another string to its bow. This is Moditope®, which goes right to the heart of subversion by preventing cancer cells from suppressing the immune system.
This would obviate the need for checkpoint inhibitors and, again in mouse models, it has shown exceptional promise and Scancell would like to start human trials next year.
All of this makes Scancell, whose shares are traded on AIM under the ticker SCLP, a very interesting company with products that could make a big difference both to the effectiveness of cancer treatment but also its cost.
It needs to raise its profile in the USA, where any partners are most likely to be found, but this is not the main drawback for investors right now. Scancell is running short of cash and will need plenty if it is to conduct large scale human trials.
Until the matter of financing is resolved I cannot recommend the shares. But this is certainly one to follow.