Scientists develop new mRNA vaccine to target aggressive brain cancer
A promising human clinical trial on four patients may pave the way for a new treatment of glioblastoma, an aggressive form of brain cancer.
Researchers from the University of Florida in the US developed an mRNA cancer vaccine which triggers the immune system to target the tumour.
Approximately 19,000 individuals in the EU are believed to be affected by this condition annually.
The approach to treating glioblastoma has seen little evolution since the early 2000s, primarily relying on chemotherapy, radiotherapy, and surgical interventions. The average survival duration for patients diagnosed with this condition is about 15 months.
The team published their findings in the peer-reviewed journal Cell earlier this month. The vaccine uses the immune system to fight cancers that are difficult to treat.
It employs a version of mRNA technology similar to what's used in COVID-19 vaccines but with a couple of tweaks.
For one, the vaccine uses cells from the patient's own tumour to create a personalised treatment.
Additionally, it includes a newly developed delivery system to generate a rapid immune response.
"Instead of us injecting single particles, we’re injecting clusters of particles that are wrapping around each other like onions, like a bag full of onions," senior author Elias Sayour, said in a statement.
"And the reason we’ve done that in the context of cancer is these clusters alert the immune system in a much more profound way than single particles would," he added.
Turning the immune system against the tumour
Scientists took genetic material called RNA from each patient's surgically removed tumour.
They then amplified the messenger RNA (mRNA), which contains instructions for what's inside every cell, including tumour cells.
Next, they wrapped this mRNA in special lipid nanoparticles creating a high-tech package. When these modified tumour cells were injected back into the patients' bloodstream, they looked like viruses, triggering an immune system response.
"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," Sayour said.
“That 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”.
The study is the result of encouraging findings from seven years of research that began with experiments in preclinical mouse models and progressed to a clinical trial involving ten pet dogs with advanced brain cancer.
Dogs can also develop spontaneous brain tumours that result in terminal outcomes, the researchers said.
The ten pet dogs lived a median of 139 days, while the median survival of dogs with this condition is 30 to 60 days.
Professor Duane Mitchell, co-author of the paper, said that these results were "a really important finding because oftentimes 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".
A Phase 1 clinical trial will now test the vaccine in up to 24 adult and paediatric patients to confirm the findings.
Further research is needed to find the best method to trigger the immune system while limiting potential side effects.
