Glioblastoma is one of the most deadly cancers, with few treatment options available. Now, a small human clinical trial has demonstrated an mRNA vaccine that quickly rallies the immune system to fight off the tumors, with promising results.
Glioblastoma is the most common form of brain cancer, and unfortunately it’s also the most aggressive. Treatment involves a combination of surgical removal, radiation and chemotherapy, however the disease almost always comes back. Patients usually live about a year after diagnosis, with only about 5% of patients surviving longer than five years.
A new study from the University of Florida could soon add a better option for patients – an mRNA cancer vaccine. This technology, best known for COVID-19 vaccines, has been shown to quickly alert the immune system to attack glioblastoma more effectively, in mice, dogs and now humans.
As you might remember from the heady days of 2020 and 2021, mRNA molecules are essentially natural blueprints that tell cells which proteins to produce. By engineering them to produce harmless versions of proteins associated with pathogens, the immune system can be trained to fight off the real thing if it appears. After the real-world success of these treatments during the pandemic, the possibility of adapting mRNA therapies for cancer took off, with intriguing early results.
This new version has two key advancements, the team says. First, the vaccine is personalized by using samples taken from the patient’s own tumor cells. The second is that the delivery mechanism is more complex, which ultimately produces a stronger immune reaction.
"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," said Elias Sayour, senior author of the study. "In less than 48 hours, we could see these tumors shifting from what we refer to as 'cold' – immune cold, very few immune cells, very silenced immune response – to 'hot,' very active immune response. 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."
This small, FDA-approved clinical trial was designed to test safety and feasibility, and only included four patients with glioblastoma. RNA was extracted from each patient’s tumor after it was surgically removed, then the mRNA was amplified and wrapped in the particle clusters. This was then injected into the patients, where it triggered the immune response. The team says that it’s currently too early to fully assess the clinical effects, but the patients did spend more time disease-free and survived longer than expected.
An expanded Phase I trial will be conducted next, involving up to 24 patients to determine an optimal and safe dose. Further down the line, phase 2 would involve 25 children.
The research was published in the journal Cell. The team discusses the trial in the video below.
Source: University of Florida
