RESOLVING THE LEDGER
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Certain cancers could be treated via bespoke vaccines in the not-too-distant future
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Every cancer is different. Because of that, researchers have for decades been working on personalised cancer vaccines designed to make the immune system recognise and attack cancers specific to each individual. The results have been mixed, but now a personalised cancer vaccine has produced positive results in a final-stage trial for the first time.
Moderna announced on 19 August that people who had undergone surgery to remove severe skin cancers, called melanomas, survived longer without the cancer returning or spreading to other parts of the body if they were given a personalised mRNA cancer vaccine in conjunction with another immunotherapy, compared with receiving that immunotherapy alone.
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The hope is that this personalised vaccine will work for many other types of cancer. Trials are already underway for certain kinds of lung, kidney and bladder forms of the condition . The other big mRNA company, BioNTech, is also testing personalised cancer vaccines in human trials.
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What is a cancer vaccine?
Cancers are caused by cells accumulating mutations to the point where they go rogue and start multiplying out of control. Mutations in proteins that protrude from the surface of cells also make cancer cells “look” a bit different to other cells. This allows our immune system to recognise and kill off many cancers without us ever knowing about it. But some cancers slip through the net – the idea of cancer vaccines is to teach the immune system to recognise them.
How are these vaccines made?
In the case of the Moderna vaccine, called intismeran autogene , a sample of a person’s cancer – a biopsy – is sequenced. It is then compared with their healthy blood cells to identify surface proteins on the cancerous cells that have distinctive mutations. Up to 34 are selected, and mRNAs coding for those proteins are made and put in the vaccine.
What happens next?
The cancer vaccine is injected into muscles, just like with the covid-19 mRNA vaccine. Cells in the muscles then temporarily produce the cancer proteins, triggering an immune response to them.
Why use mRNA vaccine technology?
It is possible to use other kinds of vaccines, but mRNA has two huge advantages: speed and cost. Making protein-based vaccines requires using living cells, which is time-consuming and requires many safety checks. For people with cancer, the faster a vaccine can be created, the better.
Benefits of mRNA cancer vaccines could exceed $75 billion in US alone
An analysis of ongoing trials suggests that mRNA cancer vaccines have the potential to deliver health benefits worth $75 billion each year in the US alone
What immunotherapy was the vaccine combined with for the trial?
It is a so-called anti-PD-1 therapy consisting of an antibody called pembrolizumab (Keytruda). Many cancers evolve to evade immune attack by putting up a “don’t attack me” sign. Immune cells “read” this sign with the help of a protein on their surface called PD-1.
Blocking PD-1 makes the “don’t attack me” sign invisible to immune cells, so they attack regardless. However, anti-PD-1 treatments work only if the immune system is already trying to attack a cancer, hence the advantage of combining them with a cancer vaccine to provoke that attack.
How well did the combined treatment work?
Moderna hasn’t told us yet. The company has announced only that the results of the phase III trial “demonstrate statistically significant and clinically meaningful improvements” in survival times.
The trial involved 1137 people who, after surgery to remove melanomas, were randomly assigned to get both the vaccine and pembrolizumab, or just pembrolizumab. What we do know is that in an earlier trial involving 157 people with melanoma over five years, the combination of the vaccine and pembrolizumab cut the risk of recurrence by 50 per cent and the risk of spread to other parts of the body by 60 per cent, compared with pembrolizumab alone.
When will this treatment become available?
Analysts speaking to the Financial Times say it could be approved next year. But because it is an individualised treatment, scaling up production will be much more complex than with a standard vaccine.
It also isn’t clear yet what the pricing will be – even with the help of mRNA technology, it won’t be cheap. A January report by Reuters suggested it would cost around $200,000 per treatment. No wonder Moderna’s share price is soaring.
Will this work for all cancers?
The hope is it will work for many cancers, but we will have to wait on more phase III trial results to be sure. That said, several other earlier-stage mRNA cancer vaccine trials have produced promising results. In fact, a study last year estimated that on the basis of these results, their potential health benefits could be worth around $75 billion a year in the US alone.
Are there any approved cancer vaccines already?
Not like intismeran autogene. Some sources will tell you there are three approved vaccines for treating cancer: Provenge, BCG and T-VEC.
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But Provenge is a treatment that involves removing immune cells from a person’s body, exposing them to a prostate cancer protein, then replacing them. BCG is the tuberculosis vaccine, which just happens to help treat some bladder cancers for reasons we still don’t understand. And T-VEC is a live herpes simplex virus engineered to kill cancer cells .
So only one of the three is a conventional vaccine, and its ant...
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