A personalized mRNA vaccine tested at UC San Francisco has become the first to successfully prevent the return and spread of cancer in late-stage clinical trials. The results could signal a new era of vaccines to treat a range of cancers, says UCSF Professor of Medicine Adil Daud , MD, who led the university's trial site.
Bay Area tennis pro Mark Orwig, 73, was diagnosed with melanoma in 2023. After physicians removed a tumor from his cheek, Orwig feared the cancer would return. His physician thought a clinical trial at UCSF might offer hope and referred him to Daud.
Daud is a UCSF Health melanoma specialist and directs the UCSF Melanoma Program , where he researches how tumors outsmart the immune system in hopes of developing better, more personalized medicines for the hardest-to-treat cancers.
Daud, Orwig remembers, offered him three different trials to choose from. But one, Daud told him, was groundbreaking enough that it just might revolutionize the way medicine treats cancer.
Orwig became one of about 1,140 patients to participate in a late-stage clinical trial that found that adding a personalized mRNA vaccine to existing melanoma treatment reduced patients' risks of the skin cancer returning or spreading. The trial's results, led by pharmaceutical companies Merck and Moderna, are not yet publicly available. Still, the firms' previously reported findings from an earlier phase trial showed that the combination treatment reduced the chance of recurrence by nearly half compared with patients who received standard treatment alone. The dual treatment also reduced the risk of the cancer spreading by nearly 60%.
"Cancer vaccines have been in testing for decades, and this is the first cancer vaccine that's shown proof of efficacy in a randomized controlled clinical trial," Daud says. "It's amazing news - if this works for melanoma, it could work for other cancers too."
Yesterday's federal funding, today's breakthroughs
Although cancer vaccines had been a vision for Daud's entire career, he says, technology wasn't able to tailor the injectable medications to patients' individual tumors. COVID-19 mRNA vaccines bridged that gap.
"One line of thinking is that other cancer vaccines failed because they were 'off the shelf;' I would get the same vaccine you would," he explains. "People who received these vaccines were generating immune responses, but it wasn't directed at their exact tumor type - and tumors are all different."
Federal research funding helped develop mRNA technology decades before mRNA COVID-19 vaccines helped turn the tide against that pandemic. The relative ease of manufacturing and customizing mRNA technology is why mRNA COVID-19 vaccines became powerful tools. It's also why the technology is ripe for future custom cancer vaccines.
'I had to do it for the next person'
Participants in the study were randomized to get either the personalized vaccine or a placebo shot in addition to standard care. Sorting patients like this ensures that any characteristics that could affect the study's results - such as sex or genetics - are evenly distributed between the two groups. Neither group knows for sure whether they received the vaccine and will only be told later to avoid influencing their reporting of side effects, for instance.
Orwig doesn't yet know for sure if he was given the new vaccine, but his cancer is still in remission.
And he's back on the tennis courts.
"I'm glad I did what I did," he said recently. "A lot of trials don't go anywhere. This trial is definitely going to go somewhere … and anybody that gets into the same situation I got into in the future is going to really benefit from it."
