At New York University's Perlmutter Cancer Center, researchers have demonstrated something melanoma patients have long hoped for: a personalized vaccine combined with immunotherapy can cut the risk of cancer recurrence and death by nearly half—and that protection holds steady five years later.
The finding matters because melanoma remains one of the most aggressive skin cancers, and while immunotherapy drugs like pembrolizumab have revolutionized treatment, they don't work for everyone. Cancer cells are remarkably skilled at hiding from the immune system, and over time they can develop resistance. Adding a vaccine to the mix offers a new strategy: teaching the immune system to recognize and attack cancer before it has a chance to return.
The study, called KEYNOTE-942, tested a personalized mRNA vaccine called intismeran alongside pembrolizumab in 107 melanoma patients who had undergone surgery to remove their tumors. Researchers analyzed each patient's tumor to identify 34 neoantigens—unique abnormal proteins that cancer cells produce—and designed a custom vaccine for each person. The vaccine essentially gives the immune system a detailed "wanted poster" of the specific cancer it's fighting. The results, presented at the American Society of Clinical Oncology annual meeting in Chicago on June 1 and published simultaneously in the Journal of Clinical Oncology, were striking.
After five years, 68.8 percent of patients receiving the combination therapy remained cancer-free, compared to 49.1 percent of those who received pembrolizumab alone. The vaccine-plus-immunotherapy approach also reduced the risk of cancer spreading to distant parts of the body by 59 percent. Perhaps most importantly, overall survival—meaning patients did not die from cancer or any other cause—reached 92.2 percent in the combination group, compared to 71.3 percent in the immunotherapy-only group.
Dr. Janice Mehnert, the study's senior investigator and a professor at NYU Grossman School of Medicine, emphasized what these numbers mean in human terms. "Our study offers strong evidence to melanoma patients that intismeran vaccine therapy, when used in combination with immunotherapy, can demonstrably reduce their risk of having their cancer return and improve clinical outcomes."
The approach works by harnessing T cells, the immune system's natural cancer fighters. Cancer cells typically hijack molecular checkpoints on T cell surfaces to turn off immune attacks, allowing the cancer to escape. Pembrolizumab blocks one of these checkpoints, the PD-1 protein receptor, making cancer cells visible to the immune system again. The mRNA vaccine amplifies this effect by training T cells to specifically recognize and attack the personalized neoantigens unique to each patient's tumor.
The implications extend far beyond melanoma. Dr. Mehnert noted that mRNA vaccines like intismeran could potentially work well in combination with immunotherapy for other cancers with high mutation rates that have proven difficult to treat. The vaccine is already being tested in clinical trials for lung cancer and other malignancies, and a phase 3 multicenter trial is underway to test whether intismeran works as a first-line therapy—meaning before other treatments fail.
For melanoma patients facing a disease that once meant a poor prognosis, these results suggest a new path forward. A personalized vaccine, combined with an established immunotherapy, may finally offer durable hope.