Experimental mRNA brain cancer vaccine evaluated in small trial

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A new experimental mRNA vaccine has shown promise in activating the immune system against a highly lethal type of brain tumor, according to results from a first-in-human clinical trial of four adult glioblastoma patients.

The study, which also included data from dogs with the disease, was published in Cell.

Tackling lethal brain tumors

Glioblastoma is a highly lethal type of brain tumor. Current treatments include surgery and radiation, sometimes given along with chemotherapy. But with a median survival of 15 months, more effective therapies are urgently needed.

“New treatment outcomes are needed for glioblastoma and pediatric brain tumors, the outcomes of which have not changed dramatically in several decades,” explained D.r. Elias Sayourthe lead author of the study, speaking with Technological Networks.

mRNA technology, known to many for its role in some COVID-19 vaccines, may offer a new solution. Several candidates are under evaluation in clinical trials for various types of cancer, including melanoma.

In the new study, Sayour and colleagues report their results using a new version of this glioblastoma vaccine technology, testing it both in dogs with the disease and in a small cohort of four human patients.

“Our brain tumor program has developed promising effects with other forms of brain cancer immunotherapy and we wanted to test a new mRNA vaccine design to improve responses to these difficult-to-treat diseases,” Sayour said.

Elicit immune responses

The vaccine uses mRNA and lipid nanoparticles in a similar way to some COVID-19 vaccines, but with a newly designed delivery system customized for the patient’s tumor cells.

The vaccine is produced by extracting and amplifying mRNA from the patient’s surgically removed tumor and packaging it inside lipid nanoparticles. This makes the vaccine look like a virus when injected into the patient’s bloodstream, triggering an immune response.

“Instead of injecting individual particles, we’re injecting groups of particles that wrap around each other like onions, like a bag full of onions,” Sayour said.

The vaccine was first tested in mice and then moved on to a trial with 10 dogs with terminal glioma, which has no other treatment options. Dogs with the disease typically have a median survival of 30 to 60 days, although the trial animals survived a median of 139 days.

“These vaccines have elicited strong responses against mouse gliomas with long-term survival and improved outcomes for dogs with naturally occurring forms of the human disease,” Sayour added.

The promising results from the dog study paved the way for a small trial with four human patients approved by the US Food and Drug Administration (FDA), with the goal of evaluating its safety before moving on to larger trials. The trial was too early to evaluate the vaccine’s clinical effectiveness, but patients lived free of the disease or survived longer than expected.

“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 well “Preclinical studies work. Animal studies will result in similar responses in patients,” explained study co-author Dr. David Mitchelldirector of the UF Clinical and Translational Sciences Institute and the UF Brain Tumor Immunotherapy Program.

Additional clinical trials planned

“We expect the Phase 1 clinical trial to include up to 24 adult and pediatric patients to validate the findings. Once an optimal and safe dose is confirmed, it is estimated that 25 children will be enrolled (in) Phase 2,” Sayour explained.

“We hope that this work will create a new paradigm that rapidly activates the immune system against cancer,” Sayour continued. “To win the war against cancer, the immune system needs a better head start. “We hope this approach will give the immune system the advantage it needs to win the race against rapidly evolving tumors.”

Reference: Méndez-Gómez HR, DeVries A, Castillo P, et al. RNA Aggregates Harness the Danger Response for Potent Cancer Immunotherapy. Cell. 2024.doi: 10.1016/j.cell.2024.04.003

Dr. Elias Sayour spoke with Dr. Sarah Whelan, Science Writer at Technology Networks.

About the interviewee:

Dr. Elias Sayour is an associate professor of neurosurgery and pediatrics at the University of Florida. He is also the principal investigator of the RNA Engineering Laboratory of the Preston A. Wells, Jr. Center for Brain Tumor Therapy and the UF Brain Tumor Immunotherapy Program. He has a medical degree from the University at Buffalo and a doctorate from Duke University.