An experimental vaccine from Moderna shows promise in keeping deadly skin cancer from returning for years, according to new clinical trial results. Subscribe to read this story ad-free Get unlimited access to ad-free articles and exclusive content.The research, presented Monday at the American Society of Clinical Oncology’s annual meeting, found that a personalized mRNA vaccine halved the risk of melanoma returning after five years. The results were also published in the Journal of Clinical Oncology.Melanoma is the deadliest form of skin cancer, and in about half of patients, the disease will come back within the first five years of treatment.“The treatments we have are not perfect. People relapse,” said Dr. Janice Mehnert, the director of the melanoma and cutaneous medical oncology program at NYU Langone Health in New York and the senior trial investigator.In the trial, 50 patients received the standard treatment: surgery, followed by a type of immunotherapy called pembrolizumab, also known as Keytruda. Another 107 patients also got a personalized vaccine tailored to their specific tumor. All of the people in the trial had at least Stage 3 melanoma, meaning the cancer had spread to nearby lymph nodes or skin and had a high risk of returning even after surgery.Five years later, nearly 70% of people in the vaccine group were cancer-free, compared to 49% of people in the standard treatment group. Adding the vaccine also cut a person’s risk of the cancer metastasizing by nearly 60%. Killing cancer cells as they appearSurgery is the first line of treatment for melanoma, with the goal of removing the entire tumor. However, undetectable cancer cells often remain in the body, so additional treatments are needed to find and eliminate these cells. Mehnert and a team of researchers across the United States and Australia have been studying whether a personalized vaccine can effectively do this.The vaccine works by training the immune system to identify and kill lingering cancer cells and later, any new cells that emerge.Each vaccine is designed using genetic material from the patient’s tumor — DNA mutations in the cancer cells that cause unique proteins to form on the cells’ surfaces. These proteins, called neoantigens, serve as the targets the vaccine trains immune cells called T-cells to attack.In the trial, each vaccine contained the information needed for the immune system to identify 34 of the top neoantigens that the scientists believed would be the best targets.Once their vaccine was ready — usually about four to six weeks after surgery — patients received up to nine doses spaced about three weeks apart. The doses aligned with their immunotherapy treatments.A paradigm shift?Jeff Coller, a professor of RNA biology and therapeutics at Johns Hopkins University in Baltimore who wasn’t involved with this research, said the results show that “the vaccine is doing exactly what we hoped it would do.”“It’s training the immune system to recognize the tumor signature long after the tumor is gone,” he said.This is not the only mRNA vaccine to show promise for preventing cancer from returning. An mRNA vaccine for pancreatic cancer also appears to reduce the risk of recurrence, according to early-stage trial results.The melanoma vaccines were in development before the Covid pandemic, but the research builds on the significant advances made in mRNA technology over the last six years. The trial was funded by Moderna and a subsidiary of Merck, which makes Keytruda.Mehnert said the results of a large-scale, phase 3 trial, which included 1,000 patients and expanded to Europe, will provide the real proof of whether personalized mRNA vaccines added to standard immunotherapy significantly reduce the risk of melanoma returning.All of the patients in the larger trial have finished treatment, and Mehnert and her team are working on compiling the results. But having promising five-year data from the study that was just published is still important, said Dr. Ravi Amaravadi, a professor of medicine at the University of Pennsylvania Perelman School of Medicine who specializes in melanoma patient care. Most cancers that are going to return do so in the first five years.If there is no recurrence within that time, “we usually stop or slow down scanning,” said Amaravadi, who was not involved with the trial.One advantage the vaccine appears to have over other therapies is low toxicity, said Dr. Shailender Bhatia, director of the melanoma team at Fred Hutch Cancer Center in Seattle, who was not involved in the study.“Generally what we have seen is that if we layer more drugs with immunotherapy, it causes more toxicity but not more benefit. So that is where the results of this trial are promising,” Bhatia said. People in the trial reported similar side effects to those from mRNA Covid vaccines — flu-like symptoms including chills and headaches — that only lasted a couple of days.Mehnert and her team found that people whose cancers did not return also had the most robust immune response post-vaccine, suggesting it is the vaccine that boosted recurrence-free survival over five years. In the future, she and her team would like to be able to develop the personalized vaccines three to four weeks after surgery to deliver the therapy earlier in the patient’s treatment. In the study, patients started receiving their vaccines during their third or fourth cycle of pembrolizumab.But first, researchers will need to see the results of the large-scale trial, Mehnert said. If that trial yields similar results, it “will be paradigm-shifting,” said Bhatia.“We have tried to use vaccines in cancer therapy for decades, but the efficacy has not been clinically relevant in phase 3 trials to date. If this is successful, this will open up a new field that will be relevant not just to melanoma, but many other cancers,” he said.