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

CNN
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When Barbara Brigham was diagnosed with pancreatic cancer in September 2020, the odds were not in her favor.

Pancreatic cancer is one of the deadliest malignancies, fatal in 88% of patients. It is also one of the most difficult to treat. The tumors can be surgically removed, but they return within seven to nine months in 90% of patients. Chemotherapy can help prolong life, but it too is rarely a cure. Radiation therapy, immunotherapy, and targeted therapies don’t work either.

Now, nearly three years after his diagnosis, Brigham says regular scans find no trace of cancer in his 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 on Wednesday in the journal Nature.

Of 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 cancer cells. None of those eight saw their cancer return.

In blood tests, all eight responders produced T-cells against their tumors, and these persisted for at least two years despite follow-up chemotherapy.

Of the eight patients who did not respond adequately to the vaccine, only two did not see their cancer come back.

“I think it’s really promising. It highlights the mRNA platform and the versatility to be able to customize or adapt these vaccines to each patient’s specific tumor and generate these personalized vaccines in a fairly short period of time,” said oncologist Dr. Neeha Zaidi at the Johns Hopkins Kimmel Cancer Center. who did not participate in the new research.

“That remains to be seen, but certainly very exciting preliminary results,” she said.

The study was not designed to test whether the vaccines would be effective. The researchers mainly focused on whether the therapy would be safe and even feasible. They also wanted to see if the three-step diet they were testing would create the desired immune responses.

The researchers were looking for a correlation between whether the vaccine worked and whether it created clinical benefit. Sometimes the drugs do what they’re supposed to do, but for some reason they don’t treat the disease.

“I think it’s really encouraging to see that [an immune] response is correlated with disease-free survival. However, this is a small study with only 16 phase one patients. So it’s a correlation. It is not causation. We need to test causation in a larger clinical trial,” said Dr. Vinod Balachandran, an oncology surgeon at Memorial Sloan Kettering Cancer Center who led the study.

He says plans for this research are already underway.

For this first study, doctors surgically removed tumors from patients and sent the tissue to a lab in Germany where scientists sequenced the genetic code from the tumors and from the patients’ blood. They compared these sets of genes to find which ones were altered in the cancer cells. After identifying the modified genes, they ran them through a computer program to let it choose which would be the most effective targets.

Then they made their custom mRNA vaccines. The patients received eight doses, which were infused into their bloodstream rather than injected into their muscles, as Covid-19 vaccines are. That’s because the researchers were trying to stimulate a slightly different part of the immune system.

“The type of immune response you want to trigger is slightly different from the type of immune response you want to trigger against a virus, where it’s mostly antibody responses, and for cancer you’re trying to actually induce T-cell responses,” Balachandran said.

Blood circulates through the lymphatic system, where lymph nodes and lymphatic organs like the spleen help make T cells.

After the eight “immuno” doses, as Brigham calls them, the patients received six months of chemotherapy. Then they received a final booster shot.

“It was not easy to get out of it. It was a little tough,” Brigham said. She tolerated the vaccine doses reasonably well but visited the hospital twice during chemotherapy.

Now she has scans every three months to check her pancreas, but so far the cancer has not returned.

However, not all the participants behaved as well as her. Eight others did not develop an adequate pool of programmed T cells in response to the vaccine, and the researchers have a theory as to why.

There are two main types of pancreatic cancer surgery, Balachandran says. One involves removal of the spleen along with the tumor.

It turns out that the mRNA vaccine concentrates in the spleen, which seems to be important for developing this large pool of tumor-attacking T cells.

When the researchers gave the vaccine to mice whose spleens had been removed, they did not respond as well as those whose spleens were 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 could be in a larger trial.

“So that’s our current working hypothesis,” he said.

Brigham says she’s just grateful she got to participate.

“I’m so grateful to have been allowed to take it,” the 77-year-old said. She recently got to watch her eldest grandson graduate from college – a moment she didn’t think she would live to see.

“The timing and timing was so perfect. It helped me, and I hope it helps someone else.