An mRNA cancer vaccine developed at the University of Florida successfully reprogrammed the immune system to combat glioblastoma, the most aggressive and lethal type of brain tumor, in the first-ever human clinical trial involving four adult patients. This vaccine also showed promising results in 10 pet dogs with naturally occurring brain tumors, whose owners consented to their participation due to lack of other treatment options.The breakthrough will now undergo testing in a Phase 1 pediatric clinical trial for brain cancer after being successfully demonstrated in preclinical mouse models. The findings, published on May 1 in the journal Cell, offer a potential new approach for enlisting the immune system in the battle against stubbornly treatment-resistant cancers. This involves utilizing an iteration of mRNA technology and lipid nanoparticles, which is similar to the technology used in COVID-19 vaccines but with two important distinctions. These distinctions include the use of the patient’s own tumor cells to create a personalized vaccine and a newly engineered complex delivery mechanism within the vaccine. According to the researchers, instead of injecting single particles, they are now injecting clusters of particles.
According to senior author Elias Sayour, M.D., Ph.D., a UF Health pediatric oncologist, the new vaccine is designed to educate the immune system about the foreign nature of tumors. The vaccine works by creating clusters of RNA wrapped around each other, which triggers a more profound immune response compared to single particles. This method, delivered intravenously, was found to quickly stimulate a strong immune-system reaction to reject the tumor, according to Sayour, the principal investigator of the RNA Engi project.
The study was conducted by a multi-institution research team, with the UF Health Cancer Center and McKnight Brain Institute leading the investigation. According to the lead researcher, the tumors observed shifted from being ‘immune cold’ with minimal immune cells and response to ‘hot’ with a very active immune response in less than 48 hours. This rapid transformation indicated that the early part of the immune system can be activated swiftly against these cancers, which is vital for unlocking the later effects of the treatment.The immune response.”
Glioblastoma is one of the most devastating diagnoses, with a median survival of around 15 months. The current standard treatment involves surgery, radiation, and a combination of chemotherapy.
The new publication represents the promising results of seven years of studies, starting with preclinical mouse models and then moving on to a clinical trial involving 10 pet dogs with terminal brain cancer and no other treatment options. The trial was conducted with the consent of the owners in collaboration with the UF College of Veterinary Medicine. Dogs offer a unique opportunity for studying this disease.Sheila Carrera-Justiz, a veterinary neurologist at the UF College of Veterinary Medicine, stated that dogs are a natural model for malignant glioma because they are the only other species to develop spontaneous brain tumors with some frequency. According to Carrera-Justiz, gliomas in dogs are always fatal. After treating pet dogs with personalized mRNA vaccines for brain cancer, Sayour’s team conducted a small FDA-approved clinical trial to test safety and feasibility before expanding to a larger trial.In a study involving four patients, RNA was taken from each patient’s own tumor that had been removed through surgery. This RNA was then used to create messenger RNA (mRNA) which contains the genetic instructions for what is inside every cell, including tumor cells. The mRNA was then placed in high-tech biocompatible lipid nanoparticles to make the tumor cells appear like a harmful virus when injected back into the bloodstream. This was done in order to trigger an immune system response. The vaccine was customized for each patient with the aim of maximizing their unique immune system. This new method demonstrates the potential of creating an mRNA cancer vaccine.The discovery that similar and strong responses can be generated across mice, pet dogs with spontaneous cancer, and human patients with brain cancer is incredibly important. According to Duane Mitchell, M.D., Ph.D., who is the director of the UF Clinical and Translational Science Institute and the UF Brain Tumor Immunotherapy Program, as well as a co-author of the paper, this finding is significant because it is often uncertain how well preclinical studies in animals will translate to similar responses in patients. Additionally, he noted that while mRNA vaccines and therapeutics have gained attention since the COVID pandemic, this method of delivering mRNA to produce these real responses is novel and unique.The immune responses seen in both animals and humans are remarkably significant and rapid. It is still too early in the trial to determine the clinical effects of the vaccine, but the initial results show that patients either lived disease-free for a longer period than expected or survived longer than expected. For example, the 10 pet dogs in the trial lived a median of 139 days, compared to the typical 30 to 60 days survival for dogs with the same condition. The next step will be to conduct an expanded Phase I clinical trial, with support from the Food and Drug Administration and the CureSearch for Children’s Cancer foundation, to include up to 24 adult and pediatric patients.Patients will be needed to confirm the results. Once an optimal and safe dose is confirmed, about 25 children will take part in Phase 2, according to Sayour, an associate professor in the Lillian S. Wells Department of Neurosurgery and the department of pediatrics in the UF College of Medicine, part of UF Health.
For the new clinical trial, Sayour’s lab will collaborate with the Pediatric Neuro-Oncology Consortium, a multi-institution consortium, to distribute the immunotherapy treatment to children’s hospitals nationwide. They will achieve this by receiving a patient’s tumor, creating the personalized vaccine at UF, and sending it back tThe UF Health Cancer Center’s Immuno-Oncology and Microbiome research program co-leader, Sayour, expressed optimism about the promising results, but also noted the continued uncertainty about effectively harnessing the immune system with minimal potential for adverse side effects. Sayour hopes that this approach could set a new standard for patient treatment and serve as a platform technology for immune system modulation. Additionally, he envisions the potential synergies with other immunotherapies and unlocking their full potential, as demonstrated in the paper.can actually complement other types of immunotherapies, so perhaps we can now use a combined approach to immunotherapy.”
Dr. Sayour and Dr. Mitchell have patents related to the vaccine, which are available for licensing through iOncologi Inc., a biotech company that originated as a “spin out” from UF and in which Dr. Mitchell has a vested interest.
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