Patients with advanced lung or skin cancer who received a COVID-19 mRNA vaccine within 100 days of beginning immunotherapy treatment lived considerably longer than those who were not vaccinated, according to new research.
Scientists from the University of Florida and the University of Texas MD Anderson Cancer Center made the discovery while studying the potential of mRNA-based therapies to activate the immune system against cancer. Their results build on more than a decade of work exploring how messenger RNA could be used to “wake up” the body’s natural defenses. The findings also move the field closer to the idea of a universal cancer vaccine that could enhance the effects of existing immunotherapy drugs.
An analysis of more than 1,000 patient records at MD Anderson provided the data behind the observation. Although the results are preliminary, researchers are now designing a randomized clinical trial to confirm them.
“Extraordinary Implications” for Cancer Care
“The implications are extraordinary — this could revolutionize the entire field of oncologic care,” said co-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. “We could design an even better nonspecific vaccine to mobilize and reset the immune response, in a way that could essentially be a universal, off-the-shelf cancer vaccine for all cancer patients.”
Jeff Coller, Ph.D., an mRNA expert and professor at Johns Hopkins University, noted that this discovery highlights another way Operation Warp Speed (the federal initiative that accelerated COVID-19 vaccine development) continues to benefit Americans in “unique and unexpected ways.”
“The results from this study demonstrate how powerful mRNA medicines truly are and that they are revolutionizing our treatment of cancer,” Coller said.
Building on Years of mRNA Innovation
Published on October 22 in Naturethe research extends Sayour’s eight years of work combining lipid nanoparticles with mRNA technology. Messenger RNA, or mRNA, is present in all cells and delivers the instructions for making proteins.
Earlier in July, Sayour’s lab reported a surprising finding: to trigger a strong immune attack on tumors, it was not necessary to target a specific protein within the cancer. Simply stimulating the immune system, similar to how it responds to a virus, could be enough to generate an antitumor effect.
In lab experiments, Sayour’s team combined their experimental “nonspecific” mRNA vaccine with a class of anticancer drugs known as immune checkpoint inhibitors. Together, the combination produced a powerful immune response in mice. The experimental vaccine itself was not directed at the COVID spike protein or any other specific molecule — it used the same underlying technology as COVID vaccines but worked more broadly.
Connecting COVID Vaccines and Cancer Treatment
That discovery, years in the making, sparked a question from former lab member and first author Adam Grippin, M.D., Ph.D., who trained at UF’s Preston A. Wells Center for Brain Tumor Therapy and now works at MD Anderson.
Would the COVID-19 mRNA vaccine work like the nonspecific vaccine?
To find out, the research team analyzed existing data from patients with Stage 3 and 4 non-small cell lung cancer and metastatic melanoma treated at MD Anderson from 2019 to 2023.
What they found was that receiving a COVID mRNA vaccine within 100 days of starting immunotherapy drugs was associated with living longer by a significant amount.
The most dramatic difference, Sayour said, was in patients not expected to have a strong immune response, based on their tumors’ molecular makeup and other factors.
As with any observational study, the findings require confirmation from a prospective and randomized clinical trial.
Nonetheless, the discovery is pivotal.
“Although not yet proven to be causal, this is the type of treatment benefit that we strive for and hope to see with therapeutic interventions — but rarely do,” said Duane Mitchell, M.D., Ph.D., Grippin’s doctoral mentor and director of the UF Clinical and Translational Science Institute. “I think the urgency and importance of doing the confirmatory work can’t be overstated.”
How the COVID Vaccine May Enhance Immunotherapy
In lung and skin cancers, doctors commonly engage the immune system with drugs designed to “release the brakes” and recognize and attack cancer cells more effectively. In advanced disease stages, however, most patients don’t respond well and often have exhausted other treatment options like radiation, surgery and chemotherapy.
The new study involved records of 180 advanced lung cancer patients who received a COVID vaccine within a 100-day period before or after starting immunotherapy drugs and 704 treated with the same drugs who did not receive the vaccine. Getting the vaccine was associated with a near doubling of median survival, from 20.6 months to 37.3 months.
Of the metastatic melanoma patients, 43 received a vaccine within 100 days of initiating immunotherapy, while 167 patients did not receive a vaccine. With the vaccine, median survival increased from 26.7 months to a range of 30 to 40 months; at the time the data were collected, some patients were still alive, meaning the vaccine effect could be even stronger.
Receiving non-mRNA pneumonia or flu vaccines resulted in no changes in longevity.
Lab Tests Support Human Data
To reinforce their observations, UF scientists conducted experiments in mice combining immunotherapy drugs with an mRNA vaccine specifically targeting the COVID spike protein. The results showed that this pairing could transform tumors that had previously resisted treatment into ones that responded, effectively stopping tumor growth.
“One of the mechanisms for how this works is when you give an mRNA vaccine, that acts as a flare that starts moving all of these immune cells from bad areas like the tumor to good areas like the lymph nodes,” Sayour said.
The next step is to launch a large clinical trial through the UF-led OneFlorida+ Clinical Research Network, a consortium of hospitals, health centers and clinics in Florida, Alabama, Georgia, Arkansas, California and Minnesota.
“One of our key motivations at OneFlorida is to move discoveries from academic settings out into the real world and the places where patients get care,” said Betsy Shenkman, Ph.D., who leads the consortium.
If confirmed, the new findings unlock numerous possibilities, and the researchers said an even better nonspecific universal vaccine could be designed. For patients with advanced cancers, the increased survival from such a universal vaccine could provide a priceless benefit: more time.
“If this can double what we’re achieving currently, or even incrementally — 5%, 10% — that means a lot to those patients, especially if this can be leveraged across different cancers for different patients,” said Sayour, an investigator with UF’s McKnight Brain Institute.
The study was funded by the National Cancer Institute and multiple foundations.
Sayour, Grippin and Mitchell hold patents related to UF-developed mRNA vaccines that are licensed by iOncologi Inc., a biotech company born as a “spinout” from UF in which Mitchell holds interest.
