The next advances in defeating cancer may come from a surprising place – our own natural defence mechanisms
Cancer, one of the most feared of all medical conditions, is often seen as an unstoppable force. But in fact, the opposite is true. It is common for our bodies to successfully eradicate early cancers without us even noticing.
By middle age, most of us probably have several microscopic tumours dotted around the body that are in the process of being destroyed by the immune system. It is only when cancers start beating our immune defences that they grow to a noticeable size and cause symptoms.
Once a tumour has reached this stage, while the immune system battle continues, the cancer is much more likely to win. Yet many scientists believe the fact that the immune system can defeat at least some early cancers suggests it could hold the secret to developing better treatments.
In the last decade or so, they have been developing a range of different measures aimed at harnessing the immune system’s cancer-killing powers.
They include genetically modified immune cells that are precision-engineered to wipe out tumours, as well as vaccines that could mean dangerous cells are killed even before they are classed as cancerous.
“Our immune systems are already doing this. We’re just giving them a bump to do it better,” said Professor Sarah Blagden, an oncologist at the University of Oxford, who is involved in this research. “This is a totally different way of thinking about cancer.”
Better survival rates
For most of medical history, cancer therapies ignored our immune systems, using more the direct approaches of surgery to cut out the tumour, then chemotherapy and radiotherapy to poison any remaining cells.
Progressive improvements to these approaches have led to better survival rates, with about half of people now surviving for at least a decade after a cancer diagnosis (see graphic), a length of time that is usually seen as signifying a cure.
We became aware of the immune system’s potential after noticing that immune cells are present inside and next to tumours, often actively fighting the tumour cells, even when someone is dying from cancer.
Pathologists have also long noted that post-mortems of people who had died from other causes sometimes reveal small tumours that had not been noticed during life, suggesting the immune system was successfully keeping them at bay.
In fact, the more detailed an examination of a certain organ takes place, the more likely it is to turn up either microscopic tumours or clumps of cells that look suspiciously pre-cancerous.
Studies have found that for instance, two in 10 women had an unnoticed breast cancer or pre-cancer at the time of death, while an estimated six in 10 men who were 80 or older had unnoticed prostate cancer.
While it is impossible to know the total number of pre-cancers we may have, “it is likely that someone in their fifties has multiple pre-cancers in their bodies that are [being] held in check”, said Professor Blagden.
The immune system’s role is usually seen as wiping out invading pathogens like bacteria and viruses, but several types of immune cells – including ones called T-cells – can recognise and destroy cancer cells, due to their mutations that let them multiply faster than usual.
Unfortunately, as cancers grow they also acquire mutations that let them evade the normal immune defences in several ways.
Indeed, one recently arrived group of cancer drugs, called checkpoint inhibitors, work by blocking proteins that act as a brake on the immune system, although these medicines do not work for everyone.
Genetically engineered immune attack
But other ways of harnessing the immune system may be more effective. One approach has given promising results for when cancer arises in cells that belong to a different branch of the immune system: B-cells, the cells that make antibodies to fight off pathogens.
In the past decade, a high-tech treatment for leukaemia involves doctors taking a blood sample from the patient, extracting their cancer-killing T-cells, and adding a gene that means they seek out and destroy B-cells.
In some patients, these altered cells, now called CAR-T cells, survive and multiply, and have been detected in the blood – still killing off the cancerous B-cells – for more than 10 years after they were injected.
“That was a really big breakthrough,” said Dr Dani Edmunds, research information manager at Cancer Research UK.
It has proven tougher to make CAR-T cells that work against solid cancers, like a breast or colon tumour, as opposed to the blood cancer leukaemia, perhaps because it is harder for them to get inside the tumour.
But this summer, a CAR-T cell therapy against cancers of the stomach was found to help people live somewhat longer – from 5.5 months to 8 months – in a small randomised trial.
While the benefit was modest, this is the first such success for CAR-T cells in solid tumours and so could be “an important step forward”, said Dr Catherine Elliott, CRUK’s director of research.
Vaccines as treatments
The immune system intervention we are most familiar with is vaccination – when we are injected with, for instance, a weakened virus, which teaches our body to fight it off when we meet the real thing.
This has inspired some scientists to try to use a similar approach to help rev up the immune response against cancer. This is called a “therapeutic vaccine” to distinguish it from the way that vaccines are usually used as prevention against illnesses, not therapies.
Several therapeutic cancer vaccines are in trials, including ones for cancers of the bowel, skin and head and neck.
In 2023, NHS England signalled that it sees cancer vaccines as so promising they should be a top research priority, by setting up a system to help patients get into a vaccine trial if there is one for their type of tumour, called the Cancer Vaccine Launch Pad.
The immense research effort that went into making Covid vaccines has helped here, with some of the cancer vaccines being based on similar technologies, including ones based on mRNA made by BioNTech.
Vaccines to stop cancer from starting
As well as therapeutic cancer vaccines, scientists such as Professor Blagden are trying to develop vaccines for cancer in the traditional sense, in that they would prevent a cancer from starting.
This aims to eliminate the cells when they have some pre-cancerous mutations but have not become a full-blown cancer. This stage may last for decades before the cells eventually accumulate enough mutations to overcome the immune attack.
The pre-cancerous mutations make the cells look slightly different to the immune system and this could be enhanced if the immune system is given a nudge by the right vaccine.
The vaccines alert the immune system to recognise several different mutations, to give the best chance of catching all pre-cancerous cells. They are being developed against cancers of the lung, breast, bowel and endometrium, the lining of the womb.
Surprisingly, just a few such vaccines may be able to protect against a much bigger number of different tumours because the same pre-cancerous mutations are involved in most of them.
“What I want to do eventually is merge all of these vaccines into one vaccine that we give the population to protect them from cancer, perhaps in their thirties or forties,” said Professor Blagden.
While it could not defeat every single type of cancer, it could perhaps prevent most.
Vaccine against all cancers
This idea of an “All Vax”, as Professor Blagden is tentatively calling it, may sound overly ambitious, but the Oxford team already has £70m of investment from two major pharmaceutical companies (which she cannot yet reveal) in their work.
And whether or not the All Vax comes to fruition, the increasing focus on pre-cancers and the immune system may yield other benefits.
For instance, a test for pre-cancers that detects the immune response to them in the blood is being developed in the hope it will work for multiple kinds of tumours. This could allow earlier treatment with better chance of a cure, said researcher Dr Victoria Goss at the University of Southampton.
A Swedish firm called Elypta is working on a urine test for multiple tumours, which gives a positive result up to five years before people get a cancer diagnosis. This may work partly by detecting the immune response.
For Professor Blagden, the only strange thing is that we have previously overlooked this area’s potential. “It’s quite shocking that this kind of prequel to cancer exists and has so far been largely ignored by medicine,” she said. “If effective, we could make cancer a disease of the past and not of the future.”
