New vaccine triggers body to fight deadly brain tumors

By Stephen Beech via SWNS

A new personalized cancer jab triggers a "fierce" immune response to fight deadly brain tumors, say scientists.

In the first-ever human clinical trials, researchers revealed that the revolutionary mRNA cancer vaccine quickly reprogrammed the immune system to attack glioblastoma - the most aggressive and lethal brain tumor.

The results of the trial involving four adult patients mirrored those in 10 pet dog patients suffering from naturally occurring brain tumors whose owners approved of their participation as they had no other treatment options, according to the American research team.

The findings, published in the journal Cell , were also similar in pre-clinical trials on mice.

Now the state-of-the-art vaccine - similar to COVID-19 jabs - is due to be tested in a pediatric clinical trial for brain cancer.

Scientists say the discovery represents a potential new way to get the human immune system to fight notoriously treatment-resistant cancers.

The vaccine combines mRNA technology and lipid nanoparticles, similar to COVID-19 jabs, but with two key differences.

The research team explained that it uses a patient’s own tumor cells to create a "personalized" vaccine, and a newly engineered complex delivery mechanism.

Study senior author Professor Elias Sayour, a pediatric oncologist of the University of Florida, pioneered the new vaccine which, like other immunotherapies, attempts to “educate” the immune system that a tumor is foreign.

Prof Sayour said: “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.

“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.”

He says that one of the most impressive findings was how quickly the new method, delivered intravenously, spurred a "vigorous" immune-system response to reject the tumor.

Prof Sayour said: “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.

“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.”

Glioblastoma is among the most devastating diagnoses, with patients only expected to survive for around 15 months. Current standard care involves surgery, radiation and some combination of chemotherapy.

The breakthrough follows seven years of study, starting in pre-clinical mouse models and then in a clinical trial involving 10 pet dogs that had spontaneously developed terminal brain cancer.

Gliomas in dogs are always terminal, according to the research team.

After treating the dogs with personalized mRNA vaccines, Prof Sayour’s team advanced the research to a small approved clinical trial designed to ensure safety and test feasibility before expanding to a larger trial.

Genetic material called RNA was extracted from each of the four patients' own surgically removed tumor, and then messenger RNA, or mRNA - the blueprint of what is inside every cell, including tumor cells - was amplified and wrapped in the newly designed high-tech packaging of biocompatible lipid nanoparticles.

That made tumor cells “look” like a dangerous virus when reinjected into the bloodstream and prompted an immune-system response.

The vaccine was personalized to each patient with a goal of getting the most out of their unique immune system.

Co-author Professor Duane Mitchell said: “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 often we don’t know how well the preclinical studies in animals are going to translate into similar responses in patients.

“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.”

While too early in the trial to assess the clinical effects of the vaccine, he said the patients either lived disease-free longer than expected or survived longer than expected.

The 10 pet dogs lived an average of 139 days, compared with a survival of 30 to 60 days typical for dogs with the condition.

Now the team is planning an expanded clinical trial to include up to 24 adult and pediatric patients to validate the findings.

Prof Savour said that, once an optimal and safe dose is confirmed, around 25 children would participate in the next phase.

Despite the promising results, he said one limitation is continued uncertainty about how best to harness the immune system while minimizing the potential for adverse side effects.

Prof Savour said: “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."

He added: “I am hopeful for how this could now synergize with other immunotherapies and perhaps unlock those immunotherapies.

"We showed in this paper that you actually can have synergy with other types of immunotherapies, so maybe now we can have a combination approach of immunotherapy.”

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