A novel cancer vaccine tailored to genetic changes in a person’s tumor is showing promise in the clinic. In a study of about 150 people who had surgery for melanoma, a type of skin cancer, those given a personalized vaccine along with an immunotherapy drug were more likely to remain free of cancer 18 months later than patients who did not receive the vaccine.

The results, reported today at the annual meeting of the American Association for Cancer Research (AACR), offer the first clear evidence that a vaccine designed to target mutations within a patient’s tumor can prevent its regrowth. That would be a milestone for the cancer vaccine field, which has struggled for decades to show results. It could also add to a growing arsenal of drugs, known as immunotherapies, that harness the immune system to fight cancer. “I was really, really excited to see these data,” says Patrick Ott of the Dana-Farber Cancer Institute, who works on similar vaccines. Although small, the new study is “a very exciting first step,” says cancer vaccine researcher Nina Bhardwaj of the Icahn School of Medicine at Mount Sinai.

Cancer vaccines aim to teach the immune system’s T cells to attack a tumor by exposing them to a protein, or antigen, that pokes out from a cancer cell. But most vaccines so far haven’t worked well because the same antigens found on tumors also appear on normal cells.

In the early 2010s, as DNA sequencing costs dropped, some scientists turned instead to sequencing the mutations in a patient’s tumor, then creating a vaccine to deliver a few of the corresponding mutated proteins, known as neoantigens, which are found only on the tumor cells. Several small trials published since 2015 by Ott’s team and others have shown that neoantigen vaccines can stimulate vaccine-specific T cells in patients with solid tumors such as melanoma, colon, lung, and brain cancer, and at least in melanoma, may curb cancer growth.

To show this more definitively, Merck and Moderna conducted a randomized trial for patients who had advanced melanoma that had spread to lymph nodes and sometimes other sites, but that had been surgically removed. All got a type of drug, known as a checkpoint inhibitor, that blocks a crucial protein from enabling tumors to evade T cells. Two-thirds also got vaccine infusions every 3 weeks for about 4 months. Like Moderna’s COVID-19 vaccine, the cancer vaccine delivered messenger RNA (mRNA) wrapped in lipid nanoparticles into cells, instructing them to make a protein—in this case, up to 34 tumor neoantigens per patient.

In December 2022, the companies made a splash when they reported that patients receiving the vaccine were 44% less likely to die or have a recurrence of their cancer. At the AACR meeting, academic collaborators shared more details: Eighty-four of the 107, or 79%, were still in remission after 18 months, compared with only 31 of 50 (62%) patients who got the checkpoint inhibitor alone. “These data give a very, very encouraging signal,” says Jeffrey Weber of NYU Langone’s Perlmutter Cancer Center, the trial’s principal investigator.

Also encouraging is that the vaccine worked regardless of how many mutations the person’s melanoma tumor had, suggesting it could work for cancer types with fewer mutations. With less to distinguish them from normal cells, such cancers tend to resist immunotherapy drugs. A larger study starting later this year aims to confirm these results and reveal whether the vaccine extends patients’ lives, measures that could encourage regulators to approve it. For now, “these [are] intriguing early findings,” says immunotherapy researcher Suzanne Topalian of Johns Hopkins University. Like other researchers, she hopes to see more details, including evidence that patients who did well made T cells specific to the neoantigens and didn’t just get an immune boost from the vaccine’s nanoparticles. Weber says those data will be reported in papers the team is submitting to journals.

Other companies are also testing neoantigen vaccines in randomized trials. BioNTech and Genentech expect to report early results this year for a neoantigen mRNA vaccine for metastatic melanoma that can’t be surgically removed—a tougher challenge partly because the patients have weakened immune systems. And Gritstone bio is testing a neoantigen mRNA vaccine against metastatic colon cancer; to boost the immune response, it is combined with a modified virus carrying the neoantigens. The Gritstone team reported in Nature Medicine in August 2022 that in several cancer patients, this resulted in “very significant numbers of T cells,” according to Bhardwaj, a promising sign of efficacy.

One of the most intriguing studies so far tested a BioNTech and Genentech neoantigen vaccine for pancreatic cancer. Investigators reported last summer that eight of 16 patients treated had T cell responses to the vaccine and were still cancer-free up to 2.5 years later. The other eight did not show an immune response and six had relapsed by 18 months. The companies plan to launch a randomized trial of that vaccine for pancreatic cancer this year.

Because pancreatic cancer cells have few mutations, “you might think is the last tumor type” that a neoantigen vaccine would work for, says trial principal investigator Vinod Balachandran of Memorial Sloan Kettering Cancer Center, who will present full details at AACR and in a paper in press. “If you can even do this in pancreatic cancer, this is very encouraging for testing personalized vaccines” for other cancers.