How Does a Personalized Cancer Vaccine Work?
Unlike a conventional vaccine that can be manufactured in the same form for millions of people, each dose of intismeran is made for one person based on the genetic characteristics of their cancer.
“The idea behind the vaccine is to take the specific tumor that is growing inside one specific patient, use DNA sequencing to understand the unique bits and pieces of that particular cancer, and create a vaccine based on that particular tumor that will trigger that person’s immune system to recognize the cancer as foreign and attack it,” says Pauline Funchain, MD, an oncologist and the associate director of cancer research training and education at the Stanford Cancer Institute in California, who isn’t involved in the development of intismeran.
Scientists analyze tissue removed during surgery and select as many as 34 abnormal proteins, called neoantigens, created by mutations in the tumor. An individualized mRNA strand then carries instructions to target those specific cancer proteins.
The goal is also to create immune memory. If microscopic melanoma cells remain after surgery, are hiding elsewhere in the body, or begin growing again months or years later, the immune system has already been taught what to look for, says Dr. Funchain.
“Using an mRNA vaccine means that we can feed the immune system very specific instructions for the unique characteristics of that person’s tumor and what exactly that particular tumor looks like,” she says.
Keytruda complements the mRNA vaccine by helping the immune system overcome PD-1 proteins so it can attack cancer cells.
It Uses the Same Basic Technology as mRNA COVID Vaccines, With a Key Difference
Messenger ribonucleic acid, mRNA for short, is a type of genetic material that the body produces naturally. mRNA molecules function as instructors, telling cells how to make proteins necessary for normal metabolic function.
mRNA vaccines became widely known through COVID-19 vaccines. With this technology, single-strand mRNA molecules deliver temporary genetic instructions that prompt the body to make specific proteins that the immune system then learns to recognize as dangerous.
“An individualized vaccine is made to stimulate the immune attack of those targets and is delivered in a lipid particle (like a soap bubble) so that it can enter cells and be expressed when injected,” Ishizuka says.
One reason this approach may be different from earlier cancer vaccines is that it isn’t one-size-fits-all. Many previous vaccines targeted the same cancer markers in everyone, while this one is designed around the unique mutations in each person’s tumor, says Funchain.
Trial Focused on People at High Risk of Melanoma Returning
Melanoma prognosis can vary considerably, depending on how far the cancer has progressed. “People who qualified for this study had stages 2B through 4, and had all tumors removed by surgery,” Funchain says. “After surgery, the likelihood of melanoma recurring [at these stages] is anywhere from 30 percent to well over 75 percent, depending on stage.”
“We don’t yet know if this strategy keeps people alive for longer or increases the long-term number of cures,” Funchain says.
Could This Lead to mRNA Vaccines for Other Cancers?
“I think these results are a critical proof of concept: for cancer vaccines, for personalized vaccines, and for mRNA as an approach,” says Ishizuka.
Melanoma has historically been an important testing ground for cancer immunotherapy. The first three approvals for modern immunotherapies were in melanoma between 2011 and 2014, Funchain says. Drugmakers then developed similar drugs for many other cancers.
“We will likely see a similar trend for mRNA vaccines in other cancers as well, particularly because mRNA-based therapies are by nature quickly adaptable,” she says.
That process has already begun. Merck and Moderna’s intismeran research program currently includes several phase 2 and phase 3 trials across several tumor types and stages, including lung, kidney, and bladder cancers, said a Merck spokesperson.
When Could the Melanoma Vaccine Be Available?
Merck and Moderna say they plan to discuss the phase 3 results with regulatory authorities, but the companies haven’t announced when they expect to apply for FDA approval.
