Personalized cancer vaccines like the ones Moderna and BioNTech are developing are tailored to each patient’s particular cancer. The researchers collect a piece of the patient’s tumor and a sample of healthy cells. They sequence these two samples and compare them in order to identify mutations that are specific to the tumor. Those mutations are then fed into an AI algorithm that selects those most likely to elicit an immune response. Together these neoantigens form a kind of police sketch of the tumor, a rough picture that helps the immune system recognize cancerous cells.
“A lot of immunotherapies stimulate the immune response in a nonspecific way—that is, not directly against the cancer,” said Patrick Ott, director of the Center for Personal Cancer Vaccines at the Dana-Farber Cancer Institute, in a 2022 interview. “Personalized cancer vaccines can direct the immune response to exactly where it needs to be.”
How many neoantigens do you need to create that sketch? “We don’t really know what the magical number is,” says Michelle Brown, vice president of individualized neoantigen therapy at Moderna. Moderna’s vaccine has 34. “It comes down to what we could fit on the mRNA strand, and it gives us multiple shots to ensure that the immune system is stimulated in the right way,” she says. BioNTech is using 20.
The neoantigens are put on an mRNA strand and injected into the patient. From there, they are taken up by cells and translated into proteins, and those proteins are expressed on the cell’s surface, raising an immune response
mRNA isn’t the only way to teach the immune system to recognize neoantigens. Researchers are also delivering neoantigens as DNA, as peptides, or via immune cells or viral vectors. And many companies are working on “off the shelf” cancer vaccines that aren’t personalized, which would save time and expense. Out of about 400 ongoing clinical trials assessing cancer vaccines last fall, roughly 50 included personalized vaccines.
There’s no guarantee any of these strategies will pan out. Even if they do, success in one type of cancer doesn’t automatically mean success against all. Plenty of cancer therapies have shown enormous promise initially, only to fail when they’re moved into large clinical trials.
But the burst of renewed interest and activity around cancer vaccines is encouraging. And personalized vaccines might have a shot at succeeding where others have failed. The strategy makes sense for “a lot of different tumor types and a lot of different settings,” Brown says. “With this technology, we really have a lot of aspirations.”
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