New mRNA cancer vaccine triggers powerful immune response against malignant brain tumor

For the first time, researchers from the University of Florida conducted a clinical trial on humans, showing that their mRNA cancer vaccine quickly reprograms the immune system to attack glioblastoma - the most aggressive and a fatal type of brain tumor.

The results of the trial in four adult patients confirm similar results obtained in 10 pet dogs suffering from naturally occurring brain tumors whose owners consented to their participation because no other treatment options were available. The breakthrough will now be tested in a Phase I clinical trial in children with brain cancer.

Published  in Cell, the results present a potentially new way to recruit the immune system to fight hard-to-treat cancers using modified mRNA technology and lipid nanoparticles similar to COVID-19 vaccines, but with two key differences: the use of the patient's own tumor cells to create a personalized vaccine and a new, complex delivery mechanism within the vaccine.

"Instead of injecting single particles, we inject clusters of particles that wrap around each other like a bag of onions," said senior author Elias Sayour, MD, PhD, a UF Health pediatric oncologist who developed the new vaccine. Like other immunotherapies, the vaccine "trains" the immune system to recognize the tumor as a foreign object.

"Among the most impressive findings was how quickly the new method, given intravenously, generated a powerful immune response to reject the tumor," Sayur said.

"In less than 48 hours, we could see these tumors go from 'cold' (with very little immune cell activity) to 'hot' (with a very active immune response)."

Glioblastoma is one of the most devastating diagnoses with a median survival of approximately 15 months. Standard treatment includes surgery, radiotherapy and a combination of chemotherapy.

The new publication is the result of seven years of research, starting with preclinical mouse models and then a clinical trial in 10 pet dogs with end-stage brain cancer, conducted with owner consent in collaboration with the UF College of Veterinary Medicine.

After treating pet dogs with personalized mRNA vaccines, Sayur's team moved on to a small-scale clinical trial approved by the Food and Drug Administration (FDA) to ensure safety and feasibility testing before expanding to a larger trial.

In a cohort of four patients, genetic material called RNA was extracted from each patient's removed tumor, and the mRNA was then amplified and packaged into high-tech biocompatible lipid nanoparticles to make the tumor cells "look" like a dangerous virus when reintroduced into the bloodstream and trigger an immune response. The vaccine was personalized for each patient to make the most of their unique immune system.

"Demonstrating that creating an mRNA vaccine for cancer in this way produces similar and potent responses in mice, pet dogs with naturally occurring cancer, and human patients with brain cancer is a truly important discovery," said Dwayne Mitchell, M.D., Ph.D., director of the UF Institute for Clinical and Translational Research and the UF Brain Tumor Immunotherapy Program and co-author of the article.

Although it is too early to assess the clinical effects of the vaccine, patients either lived longer than expected without disease or lived longer than expected.

10 pet dogs survived a median of 139 days, compared to the typical median survival of 30-60 days for dogs with this condition.

The next step, with support from the FDA and CureSearch for Children's Cancer, will be an expanded Phase I clinical trial of up to 24 adults and children to confirm the results.

Once the optimal and safe dose is confirmed, approximately 25 children will participate in Phase II.

"I'm hopeful that this could be a new paradigm for treating patients, a new platform for modulating the immune system," Sayur said.

Sayur and Mitchell have patents related to the vaccine that are in the process of being licensed by iOncologi Inc., a UF-based biotechnology company.