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In 2019, Gary Keblish got a diagnosis from his surgeon that left him stunned. The flat, dark-brown mole he’d had on his back for as long as he could remember had turned into a melanoma that was already advanced, putting him at risk of dying.
“I felt numb,” the Brooklyn teacher, 61, said in an interview.
Fortunately, Keblish was able sign on for a small clinical trial testing a preventive vaccine that might possibly keep the disease from coming back.
The trial focused on a personalized vaccine using mRNA technology that used mutations to target mutations unique to a patient’s cancer but not the healthy cells in the body. All participants in the trial would receive the immunotherapy drug Keytruda (pembrolizumab), the standard of care for high-risk melanoma patients like Keblish. Two-thirds of the participants would also receive the vaccine.
Keblish was one of those who received the vaccine — which teaches the body’s immune system to recognize cancer cells as different from normal cells so that, working along with the immunotheraoy drug, it can attack them.
After two years, Keblish’s cancer hasn’t returned.
Personalized cancer vaccine shows benefit
On Sunday, the results of the phase 2 trial, which showed that the combination of the vaccine and immunotherapy reduced the risk of recurrence by nearly half, were presented at the annual meeting of the American Association for Cancer Research.
It’s the first randomized, controlled trial to show a benefit from this type of cancer vaccine, said senior investigator Dr. Jeffrey Weber, a deputy director of NYU Langone’s Perlmutter Cancer Center and a professor of medicine at the NYU Grossman School of Medicine.
To test the effectiveness of the vaccine, the international team of researchers recruited 157 melanoma patients whose tumors had been surgically removed and who were at high risk of experiencing a recurrence of their cancers. Fifty patients received only the immunotherapy medication and 107 also got the personalized vaccination.
One of the ways cancer evades the immune system is to fool the body into thinking the threat is over, at which point the natural braking system that prevents the immune system from staying constantly on kicks in. Weber compares the way pembrolizumab works to cutting a stuck brake cable on a car so it can go forward.
Once the system’s braking system has been partially disabled, “the immune system works really well,” Weber said, adding that the downside of “cutting brake cable” is that the immune system stays turned up and some people end up with inflammation and something that resembles an autoimmune disease.
One other way cancer can avoid being destroyed is through mutations, so the immune system’s soldiers cease to recognize it as a threat.
That’s where the personalized mRNA vaccine comes in. After a patient’s tumor is removed, doctors identify proteins that are specific to that person’s tumor and no other cells in the body. As many as 34 proteins from a patient’s tumor were then the target of the vaccine.
In the trial, 40% of the patients who received only the immunotherapy drug had a recurrence of their cancer during the two-year follow-up. In comparison, 22.4% of patients who got the drug plus the vaccine had a recurrence, leading to a difference of 44% between the two groups.
The new findings are significant, said Dr. Antoni Ribas, a professor of medicine at the University of California, Los Angeles, and director of Tumor Immunology Program at UCLA’s Jonsson Comprehensive Cancer Center.
It’s the first time a cancer vaccine has been shown to have this level of benefit, close to a 50% decrease in the risk of relapse,” said Ribas. “It tells us these vaccines actually work and can turn on an immune response against the patient’s own cancer.”
The trial’s results are “very exciting,” said Dr. Thomas Marron, director of the Early Phase Trials Unit at the Tisch Cancer Institute and an associate professor of medicine at the Icahn School of Medicine at Mount Sinai in New York.
“Once the tumor is removed, we know it can come back because tiny microscopic bits have traveled elsewhere in the body and set up shop there,” Marron said. The recurrence often appears quickly, between six months and two years, he said.
The beauty of the vaccine in this study is that it targets up to 34 mutations, Marron said. “That’s like taking 34 shots on goal,” he said. You’re teaching the immune system to recognize 34 different things that are unique to that cancer.”
The researchers anticipate the phase 3 trial, scheduled to launch this summer, to show similar results. With follow-up and monitoring, it could be at least two years before data is registered with the Food and Drug Administration and up to three years before the vaccine combination would be approved for use in patients, Weber said.
Still, it’s an exciting advance in the field of cancer vaccines, particularly for stopping melanoma, the deadliest form of skin cancer, experts said.
The study is “important because it’s the first randomized study of a cancer vaccine with a clinically meaningful endpoint: stopping tumors from coming back,” said Dr. Margaret Callahan, research director of the Memorial Sloan Kettering Immunotherapeutics Program, who expressed cautious optimism about the findings.
“This is an exciting advance in the field of cancer vaccines, an area notoriously tough to make progress in,” Callahan said.
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