In 2019 Gary Keblish received a diagnosis from his surgeon that astounded him. He had a flat, dark-brown mole on his back for as long as he could remember, but it had developed into an advanced melanoma, putting his life in danger.
Keblish was able to enroll in a small clinical study evaluating a preventive vaccine that may be able to prevent the condition from returning.
The experiment concentrated on a tailored vaccination that employed mRNA technology to target mutations specific to a patient’s cancer but not the body’s healthy cells.
The immunotherapy medicine Keytruda (pembrolizumab), the standard of care for high-risk melanoma patients like Keblish, would be administered to all trial participants. The vaccine would be administered to two thirds of the participants.
Keblish was one of patients who received the vaccine, which trains the immune system to distinguish between cancer cells and healthy cells so that it can attack them in tandem with the immunotherapy medicine.
Keblish’s cancer has not reappeared after two years.
This month, during the American Association for Cancer Research’s annual meeting, the results of the phase 2 trial were announced. The trial showed that the combination of the vaccine and immunotherapy reduced the chances of recurrence by almost 50%.
According to main scientist 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, this is the first randomized, controlled experiment to demonstrate a benefit from this type of cancer vaccination.
The multinational study team gathered 157 melanoma patients who had their tumors surgically removed and were at a high risk of having their cancer return to assess the vaccine’s efficacy. 50 patients just received immunotherapy treatment, and 107 patients also received a customized immunization.
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.
The customized mRNA vaccine fills that gap. 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.
Professor of medicine at the University of California, Los Angeles and director of the Jonsson Comprehensive Cancer Center’s Tumor Immunology Program, Dr. Antoni Ribas, called the new findings remarkable.
This kind of benefit, with a nearly 50% reduction in the probability of relapse, has never before been demonstrated for a cancer vaccination, according to Ribas. It demonstrates that these vaccines are effective and have the capacity to activate an immune response against the patient’s own malignancy.
Results from the experiment are “very exciting,” according to 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.
We know the tumor can recur after removal since minute fragments have already colonized other parts of the body, according to Marron. According to him, the recurrence frequently happens between six months to two years.
According to Marron, the vaccination used in this study has the advantage of targeting up to 34 mutations. He added, “That’s like taking 34 shots on goal.” The immune system is being trained to distinguish 34 different elements specific to that cancer”.
The phase 3 experiment, set to begin this summer, is expected to provide comparable outcomes, according to the researchers. It could take at least two years for data to be registered with the Food and Drug Administration and up to three years for the vaccination combination to be licensed for use in patients with follow-up and monitoring, according to Weber.
Nevertheless, scientists said it’s a promising development in the field of cancer vaccines, particularly for preventing melanoma, the most deadly type of skin cancer.
Dr. Margaret Callahan, research director of the Memorial Sloan Kettering Immunotherapeutics Program, 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.” She also expressed cautious optimism about the results.
This is an important development in the realm of cancer vaccinations, which is notoriously difficult to advance in, according to Callahan.