GAINESVILLE, Fla. — A new vaccine undergoing human trials may finally provide a cure for the deadliest form of brain cancer. Researchers at the University of Florida have developed a personalized mRNA brain cancer vaccine which reprograms the immune system to attack glioblastoma. The results, published in the journal Cell, are giving cancer patients new hope in surviving these lethal brain tumors.
Glioblastoma is an incredibly aggressive form of brain cancer, with an average survival time of just 15 months after diagnosis. Current treatments involve surgery, radiation, and chemotherapy, but even with this multi-pronged approach, the outlook for a full recovery remains grim. That’s why the findings from this first human clinical trial are so exciting.
The new vaccine uses a similar mRNA technology to the COVID-19 vaccines that have become household names — but with a twist. Instead of delivering a pre-determined viral protein that teaches the body to recognize a virus, the new cancer vaccine is tailored to the patient’s own tumor cells. This allows the immune system to recognize and attack the specific mutations present in a patient’s cancer.
“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,” says senior study author Dr. Elias Sayour, a University of Florida Health pediatric oncologist who pioneered the new vaccine, in a media release. “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.”
Four adult patients with glioblastoma received the vaccine intravenously. The results were amazing. In just 48 hours, the tumors shifted from “cold” — meaning they had very few immune cells and a silenced immune response — to “hot,” with a very active immune response.
“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,” explains Dr. Sayour.
Before advancing to the human trial, researchers tested the vaccine using mice and a group of 10 pet dogs with spontaneously developed terminal brain cancer. Dogs are the only other species that naturally develop brain tumors with any frequency, making them a valuable resource for studying gliomas, which are universally fatal in canines. The dogs in this trial, treated with their owners’ consent, lived for an average of 139 days. That’s incredibly longer than the typical 30 and 60 days with standard treatment.
While it’s too early in the human trial to fully assess the clinical effects, the patients either lived disease-free or survived longer than expected. The next step is to expand the trial to include up to 24 adults and children with brain cancer to confirm these early findings. If the team can determine a safe dosage for patients, the experiments will move to a Phase 2 clinical trial involving 25 children.
“The demonstration that making an mRNA cancer vaccine in this fashion generates similar and strong responses across mice, pet dogs that have developed cancer spontaneously and human patients with brain cancer is a really important finding, because oftentimes we don’t know how well the preclinical studies in animals are going to translate into similar responses in patients,” notes study co-author Dr. Duane Mitchell, director of the University of Florida Clinical and Translational Science Institute and the Brain Tumor Immunotherapy Program. “And while mRNA vaccines and therapeutics are certainly a hot topic since the COVID pandemic, this is a novel and unique way of delivering the mRNA to generate these really significant and rapid immune responses that we’re seeing across animals and humans.”
What steps do cancer drugs go through to reach patients?
Developing a new drug or vaccine, including those used to treat cancer, is a complex and rigorous process that can take up to several years. This process is carefully regulated to ensure the safety and effectiveness of the drug. The process includes the following stages:
Preclinical Testing: This is the initial stage of drug development. It involves laboratory experiments to understand the drug’s effect on cancer cells. This phase includes both in vitro (in the lab, often in petri dishes) and in vivo (in animal models) testing.
Investigational New Drug Application (IND): In this step, the drug’s developers compile the results from the preclinical testing and submit an IND application to a regulatory agency such as the U.S. Food and Drug Administration (FDA).
Clinical Trials: Clinical trials involve testing the drug in humans and are generally conducted in three phases:
- Phase I: This is the first stage of testing in humans. The primary goal is to evaluate the drug’s safety, determine a safe dosage range, and identify side effects.
- Phase II: The focus here is on evaluating the drug’s effectiveness and further assessing its safety. This phase involves more participants who have the condition that the drug is intended to treat.
- Phase III: This phase involves randomized and blind testing in several hundred to several thousand patients. The aim is to confirm the drug’s effectiveness, monitor side-effects, compare it to commonly used treatments, and collect information that will allow the drug to be used safely.
New Drug Application (NDA): If the results from the clinical trials are positive, the drug’s developers can submit an NDA to the FDA (or a similar application to other national regulatory bodies).
FDA Review: The FDA then reviews the NDA. If the FDA approves the application, the drug becomes available for physicians to prescribe to patients.
Post-Marketing Surveillance (Phase IV Trials): After a drug is approved, it’s continually monitored for safety in what are known as Phase IV trials. If new side-effects or problems are detected, the FDA can choose to remove the drug from the market or change its usage guidelines.
It’s important to note that many drugs never make it through this entire process. Estimates show that for every 5,000 to 10,000 compounds that enter preclinical testing, only one is approved for patient use.
StudyFinds’ Matt Higgins contributed to this report.
