In a first-ever human clinical trial of four adult patients, an mRNA cancer vaccine developed at the University of Florida quickly reprogrammed the immune system to attack glioblastoma, the most aggressive and lethal brain tumor.
Glioblastoma is among the most devastating diagnoses, with median survival around 15 months. The current standard of care involves surgery, radiation and some combination of chemotherapy.
Microscopy of Glioblatoma
There was and is some controversy about mRNA biochemistry. mRNA has been used for many years, however the COVID 19 pandemic brought it to light. It was an innovation for mass producing vaccines on short notice.
Reported May 1 in the journal Cell, the discovery represents a potential new way to recruit the immune system to fight notoriously treatment-resistant cancers using an iteration of mRNA technology and lipid nanoparticles, similar to COVID-19 vaccines, but with two key differences: use of a patient's own tumor cells to create a personalized vaccine, and a newly engineered complex delivery mechanism within the vaccine.
"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 senior author Elias Sayour, M.D., Ph.D., a UF Health pediatric oncologist who pioneered the new vaccine, which like other immunotherapies attempts to "educate" the immune system that a tumor is foreign.
"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."
Among the most impressive findings was how quickly the new method, delivered intravenously, spurred a vigorous immune-system response to reject the tumor, said Sayour, principal investigator of the RNA Engineering Laboratory within UF's Preston A. Wells Jr. Center for Brain Tumor Therapy and a UF Health Cancer Center and McKnight Brain Institute investigator who led the multi-institution research team.
"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," he 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."
Glioblastoma is among the most devastating diagnoses, with median survival around 15 months. The current standard of care involves surgery, radiation and some combination of chemotherapy.
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