A vaccine that is injected directly into tumours could boost survival rates from hard-to-treat cancers.
The one-off jab works by reprogramming cancer cells, so they become fully exposed to the body’s immune system, which responds by releasing disease-fighting T-cells to kill off the tumour.
In tests on mice with bowel cancer, the vaccine was 100 per cent effective at completely eradicating tumours. Separate laboratory tests on human breast cancer cells produced similar results, with the vaccine resulting in their complete destruction.
For decades, cancer treatment revolved around long-established techniques such as chemotherapy – where powerful drugs are given to stop malignant cells from reproducing – and radiotherapy, when high-energy radiation is fired at tumours to destroy their DNA, halting their spread.
Chemotherapy can be very effective. But it works less well in cancer that has spread – and, as it targets both healthy and cancerous cells, it causes side-effects from nausea to hair loss and heart palpitations.
Radiotherapy on its own, meanwhile, eradicates around 40 per cent of cancers and also brings side-effects, such as skin irritation around the treatment area.
But in the past ten to 15 years, treatment of some cancers has been transformed by immunotherapy drugs. This new generation of medicines – including pembrolizumab (used to treat advanced skin, lung, bladder, breast and bowel cancers) and nivolumab (for tumours of the kidneys, head and neck) – work by taking the brakes off the immune system, so it can attack and destroy rogue, cancerous cells.
The drugs were developed because some cancer cells ‘hide’ from the body’s defences by releasing a protein, called PD-L1, which binds to the surface of immune cells, instructing them not to attack.
Immunotherapy drugs stop that protein from binding to immune cells – allowing them to identify cancer cells as foreign and launch an all-out attack on them.
The treatment has had a major impact in cancers such as malignant melanoma, an often lethal form of skin cancer, for which there used to be little treatment.
Studies show the five-year survival rate in melanoma patients on the drugs (given via weekly or fortnightly infusions into a vein in one arm) has improved by around 50 per cent since they were introduced. Many melanoma patients are still alive ten years after their diagnosis; in the 1990s, average survival time was just six months.
But while immunotherapy drugs can have dramatic effects for some patients, in others they’re of little benefit. Studies show only around 40 per cent fully respond to them. In others, tumours may shrink temporarily but start growing again weeks or months later.
This is thought to be because T-cells – the ‘killer’ cells released by the immune system – can become over-stimulated by a tumour’s presence, which weakens their ability to attack effectively.
But the new vaccine – called iVAC (intratumoural vaccination chimera) – could boost the chances of defeating cancer, according to results published in February in the journal Nature.
It works like standard immunotherapy by blocking the PD-L1 protein. But at the same time, it chemically reprogrammes cancer cells so they proactively attract the attention of killer T-cells.
It does this by making the tumour cells produce an antigen (usually a protein or fat) normally found on the surface of any type of foreign cells (such as viruses or bacteria) that get into the body. The antigen serves as a red flag to the immune system, almost inviting it to dispatch soldier cells to attack and destroy the cancer.
Although cancer cells do already produce antigens, they often give off a weak signal, helping the tumour to escape the full force of the immune system.
The new vaccine, developed by scientists at Peking University in China, turbo-charges that antigen response – so the body’s defences can react more aggressively.
The scientists who developed the vaccine plan to test it on patients in the next few years to try to boost survival from the most difficult-to-treat tumours. Which cancers the drug will be tested on first and what side-effects it may cause are as yet unclear.
Tim Elliott, a professor of immuno-oncology at the University of Oxford, said this kind of approach – using drugs that both stop immune evasion and make cancer cells attract killer T-cells – is hugely promising.
‘It combines two mechanisms in one drug and is generating a lot of excitement,’ he says. ‘A similar approach is already being investigated in trials, but with drugs given intravenously rather than injected directly into tumours.’
There are drawbacks, however. He adds: ‘Injecting the tumour is fine if there’s a single large mass. But what about when the cancer is highly disseminated in lots of tiny tumours, or when it’s small, inaccessible and hard to locate?’
Karl Peggs, a professor of cancer immunotherapy at University College London Hospitals NHS Foundation Trust, agrees. He says: ‘It’s a scientifically elegant way of delivering the two elements of treatment – nice and neat for mice experiments, but quite challenging to deliver clinically.’
