Except Bobby Kennedy Jr. has cancelled federal funding for mRNA research
By Michelle Jaffee, University of Florida
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Published in Nature Biomedical Engineering, the
University of Florida study showed that like a one-two punch, pairing the test
vaccine with common anticancer drugs called immune checkpoint inhibitors
triggered a strong antitumor response.
A surprising element, researchers said, was that they
achieved the promising results not by attacking a specific target protein
expressed in the tumor, but by simply revving up the immune system — spurring
it to respond as if fighting a virus. They did this by stimulating the
expression of a protein called PD-L1 inside of tumors, making them more
receptive to treatment. The research was supported by multiple federal agencies
and foundations, including the National Institutes of Health.
Senior author Elias Sayour, M.D., Ph.D.,
a UF Health pediatric oncologist and the Stop Children's Cancer/Bonnie R.
Freeman Professor for Pediatric Oncology Research, said the results reveal a
potential future treatment path — an alternative to surgery, radiation and
chemotherapy — with broad implications for battling many types of
treatment-resistant tumors.
“This paper describes a very unexpected and exciting
observation: that even a vaccine not specific to any particular tumor or virus
— so long as it is an mRNA vaccine — could lead to tumor-specific effects,”
said Sayour, principal investigator at the RNA Engineering Laboratory within
UF’s Preston
A. Wells Jr. Center for Brain Tumor Therapy.
“This finding is a proof of concept that these vaccines
potentially could be commercialized as universal cancer vaccines to sensitize
the immune system against a patient’s individual tumor,” said Sayour, a McKnight Brain Institute investigator
and co-leader of a program in immuno-oncology and microbiome research.
Get information about UF Health brain tumor clinical
trials here.
Until now, there have been two main ideas in cancer-vaccine development: To find a specific target expressed in many people with cancer, or to tailor a vaccine that is specific to targets expressed within a patient's own cancer.
“This study suggests a third emerging paradigm,” said Duane
Mitchell, M.D., Ph.D., a co-author of the paper. “What we found is by using
a vaccine designed not to target cancer specifically but rather to stimulate a
strong immunologic response, we could elicit a very strong anticancer reaction.
And so this has significant potential to be broadly used across cancer patients
— even possibly leading us to an off-the-shelf cancer vaccine.”
For more than eight years, Sayour has pioneered high-tech
anticancer vaccines by combining lipid nanoparticles and mRNA. Short for
messenger RNA, mRNA is found inside every cell — including tumor cells — and
serves as a blueprint for protein production.
This new study builds upon a breakthrough last year by Sayour’s lab: In a
first-ever human clinical trial, an mRNA vaccine quickly reprogrammed the
immune system to attack glioblastoma, an aggressive brain tumor with a dismal
prognosis. Among the most impressive findings in the four-patient trial was how
quickly the new method — which used a “specific” or personalized vaccine made
using a patient’s own tumor cells — spurred a vigorous immune-system response
to reject the tumor.
In the latest study, Sayour’s research team adapted their
technology to test a “generalized” mRNA vaccine — meaning it was not aimed at a
specific virus or mutated cells of cancer but engineered simply to prompt a
strong immune system response. The mRNA formulation was made similarly to the
COVID-19 vaccines, rooted in similar technology, but wasn’t aimed directly at
the well-known spike protein of COVID.
In mouse models of melanoma, the team saw promising results
in normally treatment-resistant tumors when combining the mRNA formulation with
a common immunotherapy drug called a PD-1 inhibitor, a type of monoclonal
antibody that attempts to “educate” the immune system that a tumor is foreign,
said Sayour, a professor in UF’s Lillian S. Wells Department of Neurosurgery
and the Department of Pediatrics in the UF College of Medicine.
Taking the research a step further, in mouse models of skin,
bone and brain cancers, the investigators found beneficial effects when testing
a different mRNA formulation as a solo treatment. In some models, the tumors
were eliminated entirely.
Sayour and colleagues observed that using an mRNA vaccine to
activate immune responses seemingly unrelated to cancer could prompt T cells
that weren’t working before to actually multiply and kill the cancer if the
response spurred by the vaccine is strong enough.
Taken together, the study’s implications are striking, said
Mitchell, who directs the UF Clinical and Translational Science Institute and
co-directs UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy.
“It could potentially be a universal way of waking up a
patient’s own immune response to cancer,” Mitchell said. “And that would be
profound if generalizable to human studies.”
The results, he said, show potential for a universal cancer
vaccine that could activate the immune system and prime it to work in tandem
with checkpoint inhibitor drugs to seize upon cancer — or in some cases, even
work on its own to kill cancer.
Now, the research team is working to improve current
formulations and move to human clinical trials as rapidly as possible.
Access information about UF Health's ongoing brain tumor
clinical trials here
