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

CNN
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When Barbara Brigham was diagnosed with pancreatic cancer in September 2020, the odds weren’t in her favor.

Pancreatic cancer is one of the deadliest malignancies, with 88% of patients dying. It is also one of the most difficult to treat. The tumor can be surgically removed, but in 90% of patients he will recur within 7-9 months. Chemotherapy helps prolong life but is rarely curative. Radiation, immunotherapy, and targeted therapy are also ineffective.

Today, nearly three years after his diagnosis, Brigham says routine scans found no trace of cancer in his pancreas. She credits an treatment being tested by BioNTech, one of the companies that helped produce an mRNA vaccine for Covid-19: a personalized cancer vaccine.

Brigham was one of 16 participants in a recent test of this new technology.The results of the research published on wednesday in the journal Nature.

Of the 16 patients who were able to complete all phases of the study, 8 responded to the vaccine, teaching their immune system how to recognize and fight off cancer cells. None of these eight patients had cancer recurrence.

Blood tests showed that all eight responders generated T cells against their tumors, and they persisted for at least two years despite a follow-up course of chemotherapy.

Of the eight patients who had an inadequate response to the vaccine, only two never had their cancer come back.

“I think it’s really promising,” said Dr. Niha Zaidi, an oncologist at Johns Hopkins Kimmel Cancer Center, who was not involved in the new study.

“We don’t know that yet, but it’s certainly a very exciting interim result,” she said.

This study was not designed to test whether the vaccine is effective. The researchers primarily set out to see if the treatment was safe and viable. I wanted to

Researchers were looking for a correlation between whether a vaccine works and whether it confers clinical benefit. Sometimes drugs do what they’re meant to do, but for some reason they don’t treat the disease.

“I definitely think it’s very encouraging to see that [an immune] Response correlates with recurrence-free survival. However, this is a small study, with only 16 of his patients in Phase 1. So it’s compatible. It is not causal. We need to verify causality in large clinical trials,” said Vinod Balachandran, M.D., a cancer surgeon at Memorial His Sloan Kettering Cancer Center who led the study.

He says plans for the study are already underway.

In this first study, doctors surgically removed the patient’s tumor, sent the tissue to a German laboratory, and scientists sequenced the genetic code from the tumor and the patient’s blood. They compared these gene sets to find what changed in cancer cells. After identifying the altered genes, they ran a computer program to select the most effective targets.

Then they made a personalized mRNA vaccine. The patient received eight doses that were injected into the bloodstream rather than injected into the muscle like the COVID-19 vaccine. That’s because the researchers were trying to stimulate a slightly different part of the immune system.

“The type of immune response we want to elicit is slightly different than the type of immune response we want to elicit against viruses, mostly antibody responses, and in the case of cancer, we’re actually trying to elicit a T-cell response.” Balachandran said. He said.

Blood circulates through the lymphatic system, where lymphoid organs such as lymph nodes and the spleen help generate T cells.

After eight doses of what Brigham called “immune,” the patient underwent six months of chemotherapy. Then they got the final booster of the vaccine.

“It wasn’t easy to get over. It was a little tough,” said Brigham. She tolerated the vaccinations fairly well, but she went to the hospital twice during chemotherapy.

She now has scans every three months to check her pancreas, and so far the cancer has not returned.

However, not all participants did as well as she did. The other eight did not develop the proper pool of programmed T cells to respond to the vaccine, but the researchers have a theory as to why.

According to Balachandran, there are two main types of surgery for pancreatic cancer. One is to remove the spleen along with the tumor.

The mRNA vaccine was found to be concentrated in the spleen. This appears to be important in developing a large pool of tumors that attack T cells.

When the researchers administered the vaccine to mice that had had their spleens removed, they did not respond as well as mice with intact spleens.

Balachandran said seven of the study participants had their spleens removed, five of whom were in the group that did not respond well to the vaccine. It wasn’t statistically significant, but notes that a larger trial might show a difference.

“So this is our current working hypothesis,” he said.

Brigham said she was just grateful to be able to participate.

“I’m just grateful that I was accepted,” said the 77-year-old. She recently got to see her oldest grandson graduate from college. She never thought she would live to see the moment.

“The chance and timing were perfect. It helped me, and I hope it helps someone else.”