Vaccine ‘supercharges the immune system’ to destroy ‘up to 60% of hard-to-treat tumours in the breast and lungs’
- CAR-T cell therapy programmes a patient’s immune cells to destroy tumours
- Does not work as well in solid tumours, such as those in the lung or breasts
- Jab boosts tumour-fighting cells, allowing more to penetrate stubborn tumours
Scientists have developed a vaccine that could ‘supercharge’ the immune system in its fight against cancer.
Leukaemia is increasingly being treated by CAR-T cell therapy, which involves programming a patient’s immune cells to destroy tumours.
However, this approach does not work as well in solid tumours, which do not contain cysts or liquid. Examples include cancers of the lung or breasts.
Scientists in the US have created a jab that boosts a patient’s cancer-fighting T cells, allowing more of them to penetrate stubborn solid tumours.
When cancer-ridden mice were given the vaccine alongside CAR-T cell therapy, the duo treatment completely eliminated solid tumours in 60 per cent of the animals.
The mice were even able to fight off recurring tumours months after they were given the jab. This suggests it stimulates the production of ‘memory cells’ that are primed to recognise and attack cancer.
Although early days, the US researchers hope to test the vaccine in human patients in as little as one year.
Scientists develop a vaccine that ‘supercharges the immune system against cancer’ (stock)
The study was carried out by Massachusetts Institute of Technology and led by Leyuan Ma, a research associate at the Koch Institute for Integrative Cancer Research.
Study author Darrell Irvine, professor of materials science & engineering and biological engineering, said: ‘By adding the vaccine, a CAR-T cell treatment which had no impact on survival can be amplified.
‘[This gives it] a complete response in more than half of the animals.’
CAR-T cell therapies involve taking a specific immune cell – known as T cells – from a patient’s blood.
These cells are then engineered in a laboratory to express a gene that codes for a specific receptor. This receptor later binds to a protein on the patient’s cancer.
Once these cells are re-infused into a patient’s blood, their immune system is ‘reprogrammed’ to recognise and fight off tumours.
The scientists speculated CAR-T cell therapy is relatively ineffective in solid tumours because the malignant masses have ‘an environment that suppresses the immune system’.
This environment ‘disarms’ T cells before they can reach a cancer cell’s receptor.
The scientists wondered if delivering a vaccine that targets the lymph nodes, which house a host of immune cells, could stimulate greater T cell production.
‘Our hypothesis was if you boosted those T cells through their CAR receptor in the lymph node, they would receive the right set of priming cues to make them more functional,’ Dr Irvine said.
‘[Then] they’d be resistant to shutdown and would still function when they got into the tumour.’
Several years ago, the same scientists discovered they could deliver vaccines to the lymph nodes more effectively by linking them to a fatty molecule called a lipid tail.
WHAT IS CAR-T CELL THERAPY?
CAR-T cell therapies are available on the NHS for children and people up to 25 with B cell acute lymphoblastic leukaemia.
The treatments involve taking a specific immune cell – known as T cells – from a patient’s blood.
T cells help the body fight infection by seeking out viruses and other pathogens, before killing them.
These cells are then engineered in the lab to express a gene that codes for a specific receptor that binds to a protein on the patient’s cancer.
Once these cells are re-infused into a patient’s blood, their immune system is ‘reprogrammed’ to recognise and fight off tumours.
CAR-T – chimeric antigen receptor T-cell – therapy is therefore customised to each patient.
It is suitable for those with advanced or worsening blood cancers that are not responding to treatment or have relapsed.
NICE – which provides guidance for the NHS – also recommends CAR-T therapy for adults with diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma.
The FDA in the US approved two CAR-T cell therapies in 2017.
One of the most common side effects is cytokine release syndrome (CRS).
CRS occurs when T cells are overstimulated and release excessive amounts of the protein cytokine.
This can lead to a dangerously high fever and a significant drop in blood pressure.
In most cases, CRS is manageable via treatment like steroids.
This tail binds to the protein albumin, which is in the bloodstream.
Linking vaccines to albumin allows the jab to ‘hitch a ride’ directly to the lymph nodes.
When tested in mice, results revealed the vaccine drastically increased the CAR-T cell response.
The rodents were first given around 50,000 CAR-T cells with no jab.
This resulted in the CAR-T cells being almost undetectable in the animals’ bloodstreams.
But when the vaccine was given the day after the CAR-T cells were infused, and again a week later, the CAR-T cells multiplied.
Two weeks after treatment, the CAR-T cells made up 60 per cent of the mice’s total T cell count.
This approach eliminated tumours in mice with breast cancer, melanoma and glioblastoma, which starts in the brain or spinal cord.
As well as fighting off the tumours in the first place, the treatment also prevented them reoccurring.
Around 75 days after treatment, the researchers injected the mice with cells that were identical to those that formed the rodents’ original tumours.
Results – published in the journal Science – revealed these cells were cleared by the immune system.
And about 50 days after that, the team injected the animals with slightly different tumour cells that did not express the antigen that the original CAR-T cells targeted.
The mice also eliminated these tumours.
This suggests that once CAR-T cells start destroying a tumour, the immune system creates ‘memory cells’ that eliminate these malignant masses if they reappear.
‘If we take the animals that appear to be cured and we re-challenge them with tumor cells, they will reject all of them,’ Dr Irvine said.
‘That is another exciting aspect of this strategy.
‘You need to have T cells attacking many different antigens to succeed, because if you have a CAR-T cell that sees only one antigen, then the tumour only has to mutate that one antigen to escape immune attack.
‘If the therapy induces new T-cell priming, this kind of escape mechanism becomes much more difficult.’
In a second part of the experiment, the researchers showed that human cells coated with CAR antigens also stimulate human CAR-T cells.
This suggests the same approach could work in human patients, the researchers claim.
The vaccine has been licensed to Elicio Therapeutics, which is looking to test it with CAR-T cell therapies that are already in development.
‘There’s really no barrier to doing this in patients pretty soon, because if we take a CAR-T cell and make an arbitrary [antigen] for it, then we don’t have to change the CAR-T cells,’ Dr Irvine said.
‘I’m hopeful that one way or another this can get tested in patients in the next one to two years.’
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