In a landmark achievement in the battle against malignant brain tumors, a revolutionary mRNA cancer vaccine has ignited a robust immune response, marking a significant advancement in the fight against glioblastoma, the most aggressive and fatal form of brain cancer. Developed at the University of Florida, this groundbreaking vaccine has exhibited promising outcomes in its inaugural human clinical trial involving four adult patients.
The efficacy of the vaccine mirrors findings from a study encompassing 10 pet dogs afflicted with naturally occurring brain tumors, as well as results observed in preclinical mouse models. This pivotal breakthrough is poised for further evaluation in a Phase I pediatric clinical trial for brain cancer.
Published in the Cell.com journal on May 1, the study unveils an innovative approach to engage the immune system in combating notoriously treatment-resistant cancers. Leveraging mRNA technology and lipid nanoparticles, akin to the mechanisms employed in COVID-19 vaccines, the vaccine boasts two pivotal distinctions: the creation of personalized vaccines utilizing the patient’s own tumor cells and a sophisticated complex delivery mechanism.
Senior author Elias Sayour, M.D., Ph.D., a pediatric oncologist at UF Health, elucidates the unique delivery approach, likening it to “injecting clusters of particles that are wrapping around each other like onions.” This method is designed to elicit a more robust immune response compared to traditional single-particle injections.
One of the most remarkable findings from the trial is the rapid activation of the immune system following intravenous administration of the vaccine. Sayour remarks, “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.” This swift immune activation holds immense promise for combating the aggressive nature of glioblastoma.
Glioblastoma poses a formidable challenge, with a median survival rate of approximately 15 months under current treatment protocols involving surgery, radiation, and chemotherapy. The culmination of seven years of rigorous translational research illuminates the significance of this breakthrough, spanning from preclinical mouse models to clinical trials involving pet dogs.
Sheila Carrera-Justiz, D.V.M., a veterinary neurologist at the UF College of Veterinary Medicine, emphasized the value of pet dogs as a naturally occurring model for glioma research. The transition from promising outcomes in pet dogs treated with personalized mRNA vaccines to a small FDA-approved clinical trial signifies a critical milestone in the research trajectory.
The personalized nature of the vaccine entails extracting RNA from the patient’s surgically removed tumor, amplifying the mRNA, and encapsulating it within biocompatible lipid nanoparticles. This approach aims to stimulate the immune system to recognize tumor cells as foreign entities, eliciting a robust immune response.
Duane Mitchell, M.D., Ph.D., director of the UF Clinical and Translational Science Institute, stressed the importance of translating preclinical findings into human responses. He highlighted the significance of this novel mRNA vaccine delivery method in generating rapid immune responses across animals and humans.
While it is premature to assess the vaccine’s clinical effects, preliminary results suggest extended disease-free survival in patients and prolonged survival rates in pet dogs compared to typical outcomes. The next phase involves an expanded Phase I clinical trial supported by the FDA and the CureSearch for Children’s Cancer foundation.
Upon confirmation of an optimal and safe dose, Phase II will enroll pediatric patients, with the vaccine manufactured at UF and distributed to children’s hospitals nationwide. Despite the promising results, the authors acknowledge the need to optimize immune modulation while minimizing adverse effects.
“I am hopeful that this could be a new paradigm for how we treat patients, a new platform technology for how we can modulate the immune system,” expresses Sayour. He envisions the potential synergies between this vaccine and other immunotherapies, unlocking new combination approaches in cancer treatment.
Sayour and Mitchell hold patents related to the vaccine, with licensing options by iOncologi Inc., a biotech company affiliated with the University of Florida. As the research progresses, their aim is to establish this mRNA vaccine as a transformative treatment strategy, offering renewed hope for patients facing dire prognoses.
