To treat cancer, these St. Louis researchers are looking at patients’ DNA

During the pandemic, researchers were able to construct an effective vaccine to combat COVID-19 in what seemed like record time. Some St. Louis scientists are also hoping that vaccines can be used in the fight against cancer, though with some key differences.

A team of researchers at Washington University in St. Louis are investigating how vaccines personalized to a patient’s DNA might be effective in generating an immune response that could target mutated proteins, or neoantigens, to treat certain types of cancer. The study, published this spring in the medical journal Genome Medicine, noted how this form of immunotherapy helped a 25-year-old patient with late-stage pancreatic cancer. At press time, the team has treated more than 50 patients with the personalized vaccines; they’re also documenting how the vaccines performed among approximately 20 participants with breast cancer.

“Medicine, especially cancer medicine, is moving toward personalized medicine, or precision oncology,” says Dr. William Gillanders, a Siteman Cancer Center physician and professor of surgery at Washington University School of Medicine, who was a senior author of the report. “Trying to tailor treatment to each patient based on the biology of their specific cancer and doing these sequencing analyses of patients’ cancers and then designing that precision vaccine or personalized vaccine is exciting.”

This treatment is particularly effective in cancers that are sensitive to immunotherapy, such as melanoma, lung cancer, bladder cancer, and triple-negative breast cancer. Because these vaccines are tailored for each patient using DNA, they can inform an individual’s immune system to attack harmful tumors, such as breast and pancreatic cancers, and they zero in on mutated proteins, called neoantigens, which are unique to each patient’s tumors.

The vaccines are also stable in room temperatures and relatively affordable to produce, less expensive than cellular therapy or a cellular vaccine; local researchers are making them in the Biologic Therapy Core Facility at Washington University.

At the same time, however, researching cancer vaccines is vastly different than developing a remedy for a novel coronavirus, notes Gillanders. To create a COVID-19 vaccine, researchers tested thousands of patients, with much of the general population being eligible to receive the end product. By comparison, only a small fraction of cancer patients are eligible for such a neoantigen DNA vaccine. Also, while Pfizer’s and Moderna’s vaccines were created by utilizing messenger RNA, personalized cancer vaccines are developed from DNA, a time-consuming process.

“It takes us three months to design and manufacture a vaccine for each patient,” Gillanders says. “And we can’t ask a patient to forego treatment for three months while we create a vaccine. So the biggest consideration in designing these trials to test a vaccine is trying to understand what is the best and most appropriate clinical context to use the vaccine. We want to identify patients who are potentially eligible to get these vaccines and then treat them with traditional treatments to keep their disease under control while we develop and manufacture their vaccine. Then we can use that vaccine either in combination with those treatments or at the end of those treatments.”

So if researchers are seeing progress in developing vaccines to treat cancer, is it possible that a vaccine will eventually be created to prevent cancer?

Already, Washington University researchers are testing a prevention vaccine that targets mammaglobin, which is considered to be a biomarker, or indicator, to diagnose breast cancer. Still, Gillanders says, a prevention vaccine is a considerable way away. “We’re much closer to having a treatment vaccine [on the market] than a prevention vaccine,” Gillanders says, “though there is a lot of interest.”