The vaccine caused a strong immune response in four people with fatal brain tumors

In a first-in-human clinical trial involving four adults, an mRNA cancer vaccine quickly reprogrammed the immune system to attack glioblastoma, the deadliest brain tumor, the University of Florida (UF) reported this Wednesday.

Glioblastoma is one of the most terrible diagnoses, with an average survival rate of about 15 months. The current standard of treatment includes surgery, radiation and chemotherapy.

The study results replicate those obtained in a test on 10 dogs that developed brain tumors whose owners approved their participation because no other treatment options were available, as well as a preclinical study in rats, the US university said in a statement.

“This discovery will now be tested in a phase 1 pediatric brain cancer clinical trial,” he added.

Published this Wednesday in the North American scientific journal Cell, this could be a new way to use the immune system to fight treatment-resistant cancer, because while it uses mRNA technology and lipid nanoparticles (such as Covid-19 vaccines), it uses “tumor patient cells enable the creation of a personalized vaccine” and has a “newly developed and sophisticated delivery mechanism.”

“Instead of injecting individual particles, we inject clusters, (…) they alert the immune system much more deeply than isolated particles,” said Elias Sayour, a pediatric oncologist at UF Health and a pioneer of the new vaccine who led the study. the statement says.

This method, like other immunotherapy methods, attempts to “teach” the immune system to consider the tumor as foreign and is administered intravenously.

Elias Sayour added that “one of the most impressive discoveries was how quickly” the new vaccine “stimulated a vigorous immune system response to reject the tumor.”

According to the researcher, “in less than 48 hours,” the immune response increased and became “very active.”

“This tells us that we were able to very quickly activate the initial part of the immune system against these cancers, and this is fundamental to unlocking the downstream effects of the immune response.”

The new publication is the culmination of “promising results” obtained by Sayur’s team over seven years of research.

With approval from the Food and Drug Administration (FDA), the researchers conducted this small clinical study to ensure the safety and feasibility of the tests before conducting a larger study.

“Demonstrating that creating an mRNA vaccine against similar malignancies causes similar and strong responses in mice, dogs (…) and people with brain cancer is a really important discovery because we often don’t know to what extent the preclinical results from the animal study will lead to similar responses in patients,” said Duane Mitchell, director of the UF Institute for Clinical and Translational Sciences and the Brain Tumor Immunotherapy Program at the same university and co-author of the paper.

“And while mRNA vaccines and therapeutics have certainly been on the agenda since the Covid pandemic, this is a new and unique way to deliver mRNA to generate truly meaningful and rapid immune responses,” he added.

The scientists note that although it is premature to assess the clinical effects of the vaccine, patients lived without disease longer than expected or survived longer than expected.

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

The next step, with support from the FDA and the CureSearch for Children’s Cancer Foundation, is an expanded Phase 1 clinical trial of up to 24 adult and pediatric patients to test the results.

Once the “optimal and safe dose” is confirmed, Sayur said, it will move to the second phase, which will include about 25 children.

Despite the promising results, the authors caution that there remains uncertainty about how best to harness the immune system while minimizing the likelihood of adverse side effects.