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, circumstances were not in her favor.

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

Today, nearly three years after her diagnosis, Brigham says routine scans show no trace of cancer in her pancreas. She credits an experimental therapy — a personalized cancer vaccine — that is being tested by BioNTech, one of the companies that helped create 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.

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 have seen their cancer return.

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

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

“I think this is really promising. It highlights the versatility of being able to personalize or optimize these vaccines for the mRNA platform and each patient’s specific tumor, and to generate these customized vaccines in a fairly short amount of time.” ,” said Dr. Neha Zaidi, 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 was not designed to test whether the vaccines would be effective. Researchers mostly set out to see if the therapy would be safe and feasible. They also wanted to see whether the three-phase diet they were testing would produce the desired immune response.

The researchers were looking for any correlation between whether the vaccine worked and whether it produced a clinical benefit. Sometimes, medicines do what they’re supposed to do, but for whatever reason, they don’t cure the disease.

“I think it’s certainly very encouraging to see [an immune] Feedback is related to repetition-free existence. However, this is a small study with only 16 patients in phase one. So it is correlation. This is not the reason. We need to test causality in a larger clinical trial,” said Dr. Vinod Balachandran, cancer surgeon at Memorial Sloan Kettering Cancer Center, who led the study.

He says plans for that research are already in the works.

For this first study, doctors surgically removed patients’ tumors and sent the tissue to a laboratory in Germany, where scientists sequenced the genetic code from the tumors and patients’ blood. They compared those sets of genes to find those that were altered in cancer cells. After identifying the altered genes, they ran them through a computer program to identify the most effective targets.

Then they made their individual mRNA vaccines. Patients received eight doses, which were put into their bloodstream rather than injected into their muscles, as with the COVID-19 vaccine. This is because the researchers were trying to stimulate a slightly different part of the immune system.

“The type of immune response you want to get is a little bit different than the type of immune response you want to get against a virus, where it’s mostly antibody responses, and for cancer, you really don’t -try to induce cell responses,” said Balachandran.

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

After eight “immuno” doses, as Brigham calls them, the patients received six months of chemotherapy. Then he got the last booster of the vaccine.

“It was not easy to get through. It was a little difficult,” Brigham said. She tolerated the vaccine dose well but went to the hospital twice during chemotherapy.

Now, she has scans every three months to check on her pancreas, but so far the cancer hasn’t returned.

However, not all participants performed as well as he did. 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, says Balachandran. One involves removing the spleen along with the tumor.

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

When the researchers gave the vaccine to mice whose spleens had been removed, they did not respond the way they did if their spleens were intact.

Balachandran said that seven people who took part in the study had their spleens removed and five of them were in the group that was not affected by the vaccine. They noted that the difference was not statistically significant in this small study, but it might be in a larger trial.

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

Brigham says she’s grateful she was able to participate.

“I’m so grateful to be allowed to take it,” says the 77-year-old. She was recently able to see her oldest grandson graduate from college—a moment she didn’t think she’d live to see.

“The opportunity and the timing were so right. It helped me, and I hope it helps someone else.

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