An mRNA vaccine that programs the body to fight pancreatic cancer shows early promise

When Barbara Brigham was diagnosed with pancreatic cancer in September 2020, the odds were not in her favor.Pancreatic cancer is one of the most lethal malignancies, fatal in 88% of patients. It is also one of the hardest to treat. Tumors can be surgically removed, but they come back within seven to nine months in 90% of patients. Chemotherapy can help prolong life, but it too is rarely a cure. Radiation, immunotherapy and targeted therapies also don’t work.Today, nearly three years after her diagnosis, Brigham says regular scans find no trace of cancer in her pancreas. She credits an experimental therapy — a personalized cancer vaccine — being tested by BioNTech, one of the companies that helped make the mRNA vaccines for COVID-19.Brigham was one of 16 participants in a recent test of the new technology. The results of the study were published Wednesday in the journal Nature.Half of patients respondedOf the 16 patients who were able to complete all phases of the study, eight responded to the vaccine, which taught their immune systems how to recognize and fight off the cancer cells. None of those eight has seen their cancer return.In blood tests, all eight responders made T-cells against their tumors, and those have persisted for at least two years despite a followup course of chemotherapy.Among the eight patients who did not respond adequately to the vaccine, just two have not seen their cancer return.”I think it’s really promising. It highlights the mRNA platform and the versatility to be able to personalize or tailor these vaccines to each patient’s specific tumor and generate these customized vaccines in a fairly short amount of time,” said Dr. Neeha Zaidi, an oncologist at Johns Hopkins Kimmel Cancer Center who was not involved in the new research.”It remains to be seen, but certainly very exciting preliminary results,” she said.The study wasn’t designed to test whether the vaccines would be effective. Researchers mostly set out to see whether the therapy would be safe and even feasible. They also wanted to see if the three-stage regimen they were testing would create the desired immune responses.The researchers were looking for any correlation between whether the vaccine worked and whether it created a clinical benefit. Sometimes, drugs do what they’re supposed to do, but for whatever reason, they don’t treat the disease.”I think it’s definitely very encouraging to see that response correlates with recurrence-free survival. However, it is a small study with only 16 patients in phase one. So it is a correlation. It’s not causation. We do have to test causation in a larger clinical trial,” said Dr. Vinod Balachandran, a cancer surgeon at Memorial Sloan Kettering Cancer Center who led the study.He says plans for that research are already in the works.Boosting T-cellsFor this first study, doctors surgically removed the patients’ tumors and sent the tissue to a lab in Germany where scientists sequenced genetic code from the tumors and from the patients’ blood. They compared those sets of genes to find the ones that were altered in the cancer cells. After they identified the changed genes, they ran them through a computer program to let it pick the ones that would make the most effective targets.Then they made their personalized mRNA vaccines. Patients got eight doses, which were infused into their bloodstream rather than injected into their muscles, as the Covid-19 vaccines are. That’s because researchers were trying to stimulate a slightly different part of the immune system.”The type of immune response you want to elicit is slightly different from the type of immune response that you want to elicit against a virus, where it’s mostly antibody responses, and for cancer, you try to actually induce T-cell responses,” Balachandran said.Blood circulates through the lymph system, where lymph nodes and lymph organs like the spleen help make T-cells.After the eight “immuno” doses, as Brigham calls them, the patients got six months of chemotherapy. Then they got a last booster of the vaccine.”It wasn’t easy to get through. It was a little difficult,” Brigham said. She tolerated the vaccine doses pretty well but did go to the hospital twice during chemotherapy.Now, she has scans every three months to check her pancreas, but so far, the cancer has not returned.The spleen may be keyNot all of the participants fared as well as she did, though. Eight others didn’t develop an adequate pool of programmed T-cells in response to the vaccine, and the researchers have a theory about why.There are two main types of pancreatic cancer surgery, Balachandran says. One involves the removal of the spleen along with the tumor.It turns out that the mRNA vaccine concentrates in the spleen, which seems to be important to developing that large pool of tumor-attacking T-cells.When researchers gave the vaccine to mice that had had their spleens removed, they didn’t respond as well as the ones with their spleens intact.Seven of the study participants had had their spleens removed, and five of them were in the group that didn’t respond well to the vaccine, Balachandran said. He notes that in this small study, the difference was not statistically significant, but it might be in a larger trial.”So this is our current working hypothesis,” he said.Brigham says she is just thankful she could participate.”I am just so grateful to have been allowed to take it,” the 77-year-old says. She was recently able to watch her oldest grandchild graduate from college — a moment she didn’t think she’d live to see.”The opportunity and timing was so perfect. It helped me, and I hope it helps someone else.”