Glioblastomas are one of the most aggressive cancers.
A new personalised cancer jab triggers a ‘fierce’ immune response to fight deadly brain tumours, say scientists.
In world-first human trials, researchers revealed that their revolutionary mRNA cancer vaccine quickly reprogrammed the immune system to attack glioblastoma – the most aggressive and lethal brain tumour.
The results of the trial involving four adult patients mirrored those in 10 pet dog patients suffering from naturally occurring brain tumours. Their owners approved their participation as they had no other treatment options, according to the American research team.
The findings, published in the journal Cell, were also similar in pre-clinical trials on mice.
Scientists say the discovery represents a potential new way to get the human immune system to fight notoriously treatment-resistant cancers.
The vaccine combines mRNA technology and lipid nanoparticles, similar to Covid jabs, but with two key differences.
The research team explained that it uses both a patient’s own tumour cells to create a ‘personalised’ vaccine, and a newly engineered complex delivery mechanism.
Study senior author Professor Elias Sayour, from the University of Florida, pioneered the new vaccine which, like other immunotherapies, attempts to ‘educate’ the immune system that a tumour is foreign, and should be attacked.
Genetic material called RNA was extracted from each of the four patients’ own surgically removed tumours, and then messenger RNA, or mRNA – the blueprint of what is inside every cell, including tumour cells – was amplified and wrapped in newly designed high-tech packaging of biocompatible lipid nanoparticles.
Glioblastomas are the most aggressive form of brain tumour, also known as grade 4 tumours. Grades 1 and 2 are usually not cancerous and generally glow slowly, while grades 3 and 4 are more advanced.
They are a type of glioma, meaning a tumour that grows from a glial cell. These cells come in three different forms, but it s astrocytes that can mutate into glioblastoma.
Symptoms can be hard to pin down because they depend on where in the brain the tumour is growing, but they can include:
Source: The Brain Tumour Charity
That made the tumour cells ‘look’ like a dangerous virus when reinjected into the bloodstream, prompting an immune-system response.
The vaccine was personalised to each patient with a goal of getting the most out of their unique immune system.
Professor Sayour said that one of the most impressive findings was how quickly the new method, delivered intravenously, spurred a ‘vigorous’ immune-system response to reject the tumour.
‘In less than 48 hours, we could see these tumours shifting from what we refer to as “cold” – immune cold, very few immune cells, very silenced immune response – to “hot”, very active immune response.
‘[It] was very surprising given how quick this happened, and what that told us is we were able to activate the early part of the immune system very rapidly against these cancers, and that’s critical to unlock the later effects of the immune response.’
Glioblastoma is among the most devastating diagnoses, with patients only expected to survive for around 15 months. Current standard care involves surgery, radiation and some combination of chemotherapy.
The breakthrough follows seven years of study, starting in pre-clinical mouse models and then in a clinical trial involving 10 pet dogs that had spontaneously developed terminal brain cancer.
Gliomas in dogs are always terminal, according to the research team.
After treating the dogs with personalised mRNA vaccines, Professor Sayour’s team advanced the research to a small approved clinical trial designed to ensure safety and test feasibility before expanding to a larger trial.
Co-author Professor Duane Mitchell said: ‘The demonstration that making an mRNA cancer vaccine in this fashion generates similar and strong responses across mice, pet dogs that have developed cancer spontaneously and human patients with brain cancer is a really important finding, because often we don’t know how well the preclinical studies in animals are going to translate into similar responses in patients.
‘And while mRNA vaccines and therapeutics are certainly a hot topic since the Covid pandemic, this is a novel and unique way of delivering the mRNA to generate these really significant and rapid immune responses that we’re seeing across animals and humans.’
While too early in the trial to assess the clinical effects of the vaccine, he said the patients either lived disease-free longer than expected or survived longer than expected.
The 10 pet dogs lived an average of 139 days, compared with a survival of 30 to 60 days typical for dogs with the condition.
Now the team are planning an expanded clinical trial to include up to 24 adult and paediatric patients to validate the findings.
