GoKawiilSkin cancer cells viewed under a microscope. Such images can reveal how the cancer spreads.Credit: NCI Center for Cancer Research/NCI/SPL
The announcement on 19 August that people with melanoma who received a personalized vaccine lived longer without a cancer recurrence than those who didn’t have the vaccine is a sensation for the field. The results from pharmaceutical companies Merck, in Rahway, New Jersey, and Moderna, which is headquartered in Cambridge, Massachusetts, also made a big splash among researchers and people with cancer more widely.
What makes the findings so exciting and important is that they came from a large, late-stage phase III trial — a double-blind, placebo-controlled test involving more than 1,100 participants. It comes after a successful phase II trial in 2024, with just 157 participants (J. S. Weber et al. Lancet 403, 632–644; 2024). This latest study gives greater confidence that the vaccine, called intismeran, works, and brings it a step closer to gaining regulatory approval.
Moderna cancer vaccine stops melanoma returning: what’s next for personalized treatments?
If intismeran is approved, it will become the first cancer vaccine available for people with melanoma and only the second therapeutic cancer vaccine, following the US Food and Drug Administration’s approval in 2010 of sipuleucel-T for advanced prostate cancer.
And the implications are wider. Because all cancers involve mutations in a cell’s DNA, personalized cancer vaccines, which target mutations that are specific to a tumour, could have broad applicability across cancers. Several phase II and phase III trials testing intismeran in people with melanoma, lung cancer, bladder cancer and kidney cancer are ongoing. And previous clinical trials testing other personalized vaccines have also had encouraging results.
The promise that cancer vaccines could soon be in use will lead to renewed interest and investment, accelerating discovery and advancing the field. The concept is attractive, being analogous to vaccination against infectious diseases. And there are ample opportunities to enhance cancer-vaccine efficacy further.
Such vaccines work by delivering tumour antigens to a person’s body. These antigens are often small pieces of protein on cancer cells. They act like flags, helping the immune system to recognize that something is wrong and to respond by eradicating the cells.
How personalized cancer vaccines could keep tumours from coming back
For decades, clinical trials have shown that cancer vaccines can trigger immune responses against cancer cells, but unequivocal proof of clinical efficacy has been elusive, until now. The majority of tumour mutations encoding antigens that stimulate a strong immune response are unique to an individual, thus requiring a custom-made vaccine for each person. And this is costly and time-consuming. The feasibility and safety of personalized cancer vaccines targeting tumour mutations were first demonstrated about ten years ago by our group and others (P. A. Ott et al. Nature 547, 217–221; 2017).
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