An experimental vaccine developed by Merck and Moderna could become the first vaccine of its kind used to treat cancer. Scientists hope it won’t be the last.
On Thursday, the drug makers announced that patients with melanoma who received a vaccine tailored to help their immune systems attack their tumors were 42 percent less likely to experience a recurrence of the cancer within two years than those who did not receive the vaccine. The companies have yet to show the treatment can prolong melanoma patients’ overall survival.
The results come at a time of great momentum in the development of cancer vaccines — an idea scientists have tried and failed to realize for decades.
“There have been thousands of papers written on therapeutic cancer vaccines,” said Dr. Steven Rosenberg, chief of the surgery branch at the National Cancer Institute and a pioneer of immunotherapy, the use of the body’s immune system to fight cancer.
Buoyed by recent scientific advances, however, researchers are now testing whether such vaccines could one day be used for a range of cancers, including hard-to-treat ones like pancreatic and brain cancer. Those efforts have been bolstered by investments from drug makers like Moderna as well as hospitals like Memorial Sloan Kettering Cancer Center, which in 2024 established a center dedicated to designing, producing and administering cancer vaccines on site. This year, the federal government also announced a $200 million public-private partnership to advance these vaccines.
There is still reason for skepticism. It’s unclear, for example, whether other cancers will respond to this approach as favorably as melanoma, a cancer that is easier to target with, and particularly responsive to, therapies that harness the immune system.
“This is the first step,” said Dr. Robert Vonderheide, president-elect of the American Association for Cancer Research and director of the Abramson Cancer Center at the University of Pennsylvania. “Will it work in other tumors? I’m hopeful. Do we have a lot to learn? For sure.”
A Century-Old Idea
The notion that a person’s own immune system could fight off cancer has been around for a long time — more than a century, some say, citing efforts in the 1890s to treat cancer with bacterial mixtures.
A few major developments have changed the field, though. For one, scientists came to understand that tumors produce “neoantigens,” new proteins that distinguish tumor cells from healthy cells — somewhat akin to an enemy flag. In the last 20 years, a significant reduction in the cost of genetic sequencing has made it easier than ever for scientists to identify these flags by sequencing tumor DNA.
At the same time, the technology to predict which flags were most likely to provoke an immune system attack was improving. The idea of a cancer vaccine like Merck and Moderna’s is to deliver a bespoke set of these enemy flags, customized to an individual’s tumor, to teach the immune system to recognize them and attack if the cancer reappears.
And thanks to the successes in Covid vaccine development, it is now relatively cheap and easy to make vaccines using mRNA, which carry instructions for the body to make these neoantigens. The Moderna and Merck vaccine uses this approach, though scientists are also exploring others.
The companies delivered their vaccine in combination with pembrolizumab (Keytruda). The medication is part of a relatively new class of drugs called immune checkpoint inhibitors, which take the brakes off important immune cells so they can attack cancer cells once they recognize them.
“Having all of those capabilities all kind of converge at the same time led to a lot of excitement and a lot of opportunity for innovation,” said Dr. Catherine Wu, head of stem cell transplantation and cellular therapies at Dana-Farber Cancer Institute in Boston. Dr. Wu led one of the first promising studies of a personalized cancer vaccine for melanoma.
The Merck-Moderna melanoma vaccine trial built on those efforts. The trial involved 1,137 melanoma patients, about two-thirds of whom were randomly assigned to receive an experimental mRNA vaccine, delivered in nine doses, in addition to pembrolizumab. The other third received a placebo and pembrolizumab.
Two years after entering the trial, those who received the vaccine were far less likely to have had the cancer come back at all or, worse, spread far in the body.
“You’ve effectively immunized the body to recognize the cancer and kill it,” said Dr. Marjorie Green, head of oncology clinical development at Merck. Dr. Green said the company planned to apply for regulatory approval as soon as possible.
Ted Komenda, an avid boater, golfer and amateur novelist, was diagnosed with Stage 3 melanoma three years ago. “They said it was treatable and the outcomes were pretty good,” he said, but his own research online quickly turned up five-year survival statistics of 65 to 75 percent, “which I didn’t really deem all that great.”
When his doctors at Dana-Farber asked Mr. Komenda if he wanted to participate in the trial, he didn’t hesitate. The vaccine “was incredibly unobtrusive,” he said. The worst side effect he experienced was a brief fever. “I went to work every day — I lived my life,” he said. He received his last dose of vaccine about a year ago. Now 55, he remains cancer free.
“I’m hopeful that it continues to do its job,” he said.
Taking on Other Cancers
Scientists are studying similar vaccines in kidney, bladder and non-small-cell lung cancer, as well as pancreatic cancer and glioblastoma, a brain cancer that is notoriously difficult to treat.
But aside from the melanoma trial, the published results so far are mostly from small, observational studies. And because many are testing the vaccines’ effectiveness at preventing a cancer from coming back after it has been treated, the results aren’t obvious the way they might be with a drug that shrinks a tumor. It will take time and randomized experiments for researchers to collect enough data to determine whether these vaccines improve outcomes.
Recent randomized trials of vaccines for colon cancer and for head and neck cancer failed to hit their goals of reducing recurrence and improving the rate of progression-free survival, respectively.
One study that is being closely watched is a randomized controlled trial involving BioNTech and Genentech. The trial is testing a personalized mRNA vaccine against pancreatic cancer in 260 patients. An early study of the approach, led by Dr. Vinod Balachandran at Memorial Sloan Kettering, found that eight of 16 patients who received the vaccine showed an immune response. Seven of them were still alive four to six years later. The five-year survival rate for pancreatic cancer is about 13 percent.
Preventing Cancer Outright
Other scientists are exploring whether vaccines could go so far as to stop cancers in their tracks, or even prevent them from ever forming in the people most at risk.
One such effort is taking place at the University of Pittsburgh, where Olivera Finn, a professor of immunology and surgery, is experimenting with a vaccine that contains a synthetic version of a protein called MUC1 that is expressed by many human tumors. Dr. Finn is testing whether the vaccine can stimulate the immune response to attack tumor cells and intercept ductal carcinoma in situ, an early form of breast cancer that can sometimes spread.
Dr. Susan Domchek, a breast oncologist at the University of Pennsylvania, and Dr. Vonderheide, the A.A.C.R. president-elect, are testing a similar vaccine in people who carry the BRCA 1 or 2 mutation. Their vaccine contains three different proteins that are also common across cancers. Their hope is that such a vaccine could one day be used “off-the-shelf” to prevent a variety of cancers.
And at the MD Anderson Cancer Center in Houston, Dr. Eduardo Vilar-Sanchez, interim chair of clinical cancer prevention, is studying a prevention vaccine for otherwise healthy people with Lynch syndrome. The inherited condition vastly increases the risk of developing colorectal, endometrial and ovarian cancer. The vaccine uses a virus to deliver more than 200 proteins associated with polyps or early-stage cancers, in hopes of training the immune system to attack if a tumor does develop.
This work is still in the very early stages. It will take time and money to figure out the best approach. But, some researchers said, it’s a natural next step.
In the 1990s, cancer vaccines were tested in patients with advanced tumors to try to shrink them — but that proved too challenging a job for the immune system. So researchers moved to testing the vaccines as a way of preventing recurrence in patients who had minimal cancer left.
With new evidence that such an approach can work, some researchers are looking to what they see as the next logical extension. “Is there a way in the future that cancer vaccines can be truly preventative? That’s the conceptual part of this that gets me very excited,” Dr. Vonderheide said.
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