2024-05-01 15:11:11
An mRNA vaccine has been shown to be able to reprogram the immune system to attack glioblastoma, the most aggressive and lethal brain tumor, in the first clinical trial in four patients.
The results, which are published in the journal ‘Cell’, corroborate those obtained in an animal model, specifically 10 dogs that suffered from brain tumors whose owners approved their participation, since they had no other treatment options, as well as the results of preclinical mouse models.
The vaccine, developed at the University of Florida (USA), will be tested in a phase 1 clinical trial in patients with this brain cancer.
The discovery represents a new way to reactivate the immune system to fight treatment-resistant cancers. This is a technology that emulates mRNA and lipid nanoparticle technology, simitate COVID-19 vaccinesbut with two key differences: the use of the patient’s own tumor cells to make a personalized vaccine and a complex, newly designed delivery mechanism within the vaccine.
“Instead of injecting individual particles, we inject groups of particles that wrap around each other like onions,” explains lead researcher Elias Sayour, a pediatric oncologist and pioneer of the new vaccine. He adds that, basically, like other immunotherapies try «educate» to the immune system. And, the fact of doing with what you call ‘bag of onions‘ is precisely because “in the context of cancer, these groups alert the immune system in a much more profound way than individual particles would.”
The researchers especially highlight the How quickly the new method, administered intravenously, stimulated a potent response of the immune system to reject the tumor.
Glioblastoma is among the most devastating diagnoses, with a median survival of around 15 months
“In less than 48 hours, we were able to see these tumors go from what we call ‘cold’ (immune cold, very few immune cells, very muted immune response) to a ‘hot’ and very active immune response.”
Glioblastoma is among the most devastating diagnoses, with a median survival of around 15 months. The standard of treatment involves surgery, radiation and some combination of chemotherapy.
Seven years of studies
The new publication is the culmination of promising results over seven years of studies, starting in preclinical mouse models and then in a 10-dog clinical trial who had spontaneously developed terminal brain cancer and had no other treatment options.
Dogs offer a natural model for malignant glioma because they are the only other species that develop spontaneous brain tumors with any frequency. Gliomas in dogs are universally terminal.
After treating dogs that had spontaneously developed brain cancer with personalized mRNA vaccines, Sayour’s team conducted a small clinical trial designed to ensure safety and test feasibility before expanding to a larger trial.
In a cohort of four patients, genetic material – RNA – was extracted from each patient’s surgically removed tumor, and then the messenger RNA or mRNA (the blueprint for what is inside each cell, including tumor cells) was amplified and wrapped in the new design. It was later packaged using biocompatible lipid nanoparticle technology to make tumor cells ‘look’ like a dangerous virus when reinjected into the bloodstream and trigger an immune system response. The vaccine was customized for each patient to make the most of their unique immune system.
“The demonstration that making an mRNA cancer vaccine in this way generates similar, strong responses in mice, dogs that have spontaneously developed cancer, and human brain cancer patients is a really important finding, because we often don’t know how the vaccines work.” preclinical studies. Animal studies will result in similar responses in patients,” highlights Duane Mitchell, co-author of the article.
The vaccine was customized for each patient to make the most of their unique immune system.
Although the trial was not designed to evaluate the clinical effects of the vaccine, patients lived disease-free longer than expected or survived longer than expected.
The next step will be an expanded phase I clinical trial that will include up to 24 adult and pediatric patients to validate the findings. Once an optimal and safe dose is confirmed, an estimated 25 children will participate in Phase 2.
Despite the promising results, the authors acknowledge that one limitation is uncertainty about how to best harness the immune system while minimizing the potential for adverse side effects.
“I am hopeful that this could be a new paradigm for how we treat patients, a new technological platform for how we can modulate the immune system,” Sayour concludes.
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