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Pancreatic cancer mRNA vaccine shows lasting results in an early trial
By Kaitlin Sullivan, Marina Kopf and Anne Thompson, NBC News
Donna Gustafson had a harder time than usual shaking off the jet lag from her 22-hour journey from Florida to Australia. Two days into her trip, her skin took on the yellow hue of jaundice.
Gustafson, who is now 72 and lives in Delray Beach, Florida, went to the emergency room for fluids, thinking she was dehydrated. In a surreal moment, the Australian doctors instead told Gustafson that she had pancreatic cancer.
“They were very adamant about it,” Gustafson said. “This is absolutely pancreatic cancer.”
She and her husband, Ed, were on the next flight home. Nine days later, Gustafson had surgery to remove the Stage 2 cancer from her pancreas. The day before she was supposed to start chemotherapy, her doctors told her about a clinical trial exploring the use of personalized messenger RNA vaccines for cancer. It was February 2020 — months before mRNA vaccines for Covid would become one of the world’s hottest commodities. Very soon after, Gustafson was the first person to get one for pancreatic cancer.
“It was a no-brainer,” Gustafson said of joining the trial. “I knew that statistically, the odds were against me.”
Less than 13% of people diagnosed with pancreatic cancer live for more than five years, making it one of the deadliest cancers. There is no routine screening for pancreatic cancer, such as colonoscopy or mammogram, and symptoms typically don’t show up until the disease is advanced. Once detected, there are few options for treatment. Only about 20% of cases are operable, which is currently required for someone to be eligible to join a pancreatic cancer vaccine trial.
Donna Gustafson was diagnosed with pancreatic cancer in 2019.
Last year, she hiked Mt. Etna in Italy last year to celebrate her
50th wedding anniversary.
Photo Courtesy of Donna Gustafson
The vaccines work as a type of so-called immunotherapy, harnessing a person’s immune system to fight cancer cells. The goal is not to eliminate existing tumors, but instead to stamp out lingering, undetected cancer cells, and later any new cells that form before they can cause a recurrence.
Patients still have surgery to remove tumors. After that, the mRNA vaccines are personalized for each individual using genetic material taken from their unique tumor cells. In the clinical trial, after getting the vaccine, the patients also received chemotherapy, which is standard post-op treatment for operable pancreatic cancer.
Traditional immunotherapies can be very effective, but they only work in about 20% of all cancers, leaving the majority of cancers without immune-based treatments, said Dr. Vinod Balachandran, director of the Olayan Center for Cancer Vaccines at Memorial Sloan Kettering Cancer Center in New York City, who is leading the trial Gustafson joined.
Pancreatic cancer is the poster child for these difficult-to-treat cancers, Balachandran said, and experts have long believed that people with pancreatic cancer could not generate an immune response against tumors. But after nine doses of the personalized vaccine, Gustafson is one of eight people in the 16-person Phase 1 trial who did just that, producing an army of immune cells called T cells that seek out and destroy tumor cells.
“This is one of the hardest cancers to generate any immune response, let alone such a potent one,” Balachandran said.
Balachandran and his team published the results of the Phase 1 clinical trial last year. At the time, the patients, all of whom had early-stage disease before they joined the trial, had only been tracked for just over three years, and it was unclear whether the immune response would last and lead to the patients living longer, he said. New data collected during the trial’s six-year follow-up period shows that it may. Those findings will be presented Monday at the American Association for Cancer Research’s annual meeting in San Diego.
Six years after treatment, Gustafson and six others who responded to the treatment are still alive, along with two of the eight people who did not respond. Two of the responders, including the one who died, had a cancer recurrence; Gustafson’s cancer has not come back.
“The most important finding here is that the people who mount a response to the vaccine live longer than those who do not,” said Dr. William Freed-Pastor, a physician-scientist at Dana-Farber Cancer Institute, who was not involved with the trial. He cautioned, however, that the results come from a very small group of patients. More research is still needed.
Genentech and BioNTech, the two drugmakers behind the vaccine, have already launched a larger Phase 2 clinical trial. And Balachandran and his team are digging into the specifics of what appears to be happening in the immune system.
Their latest findings detail how two important types of T cells likely work in tandem to create a durable immune response, which is paramount for long-term survival. Early on, the team was able to see that the people who responded to the vaccines made a type of T cell called a “killer T cell.” These are the immune cells that actually attack cancer. The follow-up research found that the longevity of these immune cells appeared to be bolstered by “helper T cells” that the vaccines also appeared to prompt.
“The assumption is that for an optimal cancer vaccine response, you would want to make both,” Balachandran said.
Shifting the research
Earlier research tested mRNA vaccines to treat people with advanced cancer, with disappointing results, “so we thought we didn’t have a vaccine that would work,” said Dr. Robert Vonderheide, the president-elect of the American Association for Cancer Research and director of the Abramson Cancer Center at the University of Pennsylvania.
In reality, newer research like this Phase 1 trial suggests the immunotherapy may work in less advanced cancer.
“It’s only when we shifted our mindset that we started to see that vaccines can work in some patients,” said Vonderheide, who was not involved with the trial. “Now that we’re getting into the mechanisms of how these work, we might be able to go back and see how we could make them work in people with more advanced cancer.”
The results are promising but early, he cautioned. There is always a subgroup of people diagnosed with pancreatic cancer who survive longer than five years, which is an important thing to keep in mind with any novel therapy, Vonderheide said.
“There could be another factor underlying why some patients mount a response that could be the reason they are also surviving,” Freed-Pastor said.
Still, both Freed-Pastor and Vonderheide agreed that early results that show at least some people with pancreatic cancer can respond to immunotherapies is an important step forward in the field. Another team is working on an off-the-shelf vaccine that targets a protein called KRAS that is present in as many as 90% of pancreatic cancers. In a small, early trial, about 85% of the participants mounted an immune response to the protein.
Having multiple immunotherapies is welcome, Vonderheide said.
“The moment we have something that we think is effective, cancer cells find a way to work around it, and the solution to that is to have multiple tools to fight it,” he said.
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Charles McKinley Reynolds Jr., at 83, had led a full life: a devoted family, loyal friends, and success in business. A Type-2 diabetic, he was attentive to regular check-ups and had survived colon cancer through the guidance of his then-physician and friend, Dr. Tom Scott, and later prostate cancer, through treatment at Johns Hopkins Hospital in Baltimore.
In November 2020, Reynolds’ breathing was labored. He checked into NCH Hospital near his home in Naples, Florida, and was diagnosed with aortic stenosis, the hardening of heart valves, not uncommon in elderly patients. He was helicoptered the next day to Tampa General Hospital under orders by Dr. Guilherme Oliveria, head of Tampa General Cardiology. Expectations were Reynolds would undergo transcatheteraortic valve replacement (TAVR), a less invasive procedure than implanting a valve by open heart surgery.
The pancreas, situated behind the liver, produces hormones that assist in digestion and control of blood sugar levels. Pancreatic cancer, as in Reynolds’ case, is often detected too late to save a patient’s life.
“Charles was in great pain and suffered terribly,” Ms. Reynolds recalled. “He went to the hospital just before Thanksgiving and decided to come home after the TAVR. I said, ‘Are you sure, because you know what that means?’ He said, ‘Yes, I’ve had my talk with God and I’m ready to come home. I don’t want to die in the hospital.’ We got him home on Tuesday. By the following Saturday, the day after Christmas, he was deceased.”
“Before the valve replacement, a biopsy found stage four pancreatic cancer, meaning the cancer had spread beyond the pancreas, in this case to his liver,” explained his wife, Reesa Motley Reynolds. “Nonetheless, they did the TAVR because they thought it would help him get stronger, with better breathing and blood circulation, so he could then go to the Moffitt Cancer Center, a premiere cancer facility, and be treated for the pancreatic cancer.”
But Reynolds always was a man with vision. While still hospitalized, wife at bedside, he arranged a conference call with lifelong friend, Dr. Louis Sullivan, the first African American to head the U.S. Department of Health and Human Services and an over two-decade president of Morehouse Medical College; Dr. Scott, and a mentee, Dr. Alvin Harris, a fellow Morehouse College grad, as was Reynolds. Reynolds obtained a commitment that the quartet would launch a platform to expand research and public awareness about pancreatic cancer with a focus on pain management and, particularly, on how African Americans are affected by the disease.
“We fulfilled our promise by establishing the Charles McKinley Reynolds Jr. Pancreatic Cancer Pain Management Initiative,” Ms. Reynolds said. “From January 2021 and the following two years after Charles died, we assembled a working board of physicians, researchers, and others, and developed marketing tools. Our website debuted in January 2023.”
“In April, we were honored to join a delegation of about 40 minority health advocates and practitioners, under the auspices of the National Minority Health Quality Forum headed by its president, Dr. Gary Puckrein, to attend a White House discussion on President Biden’s Cancer Moonshot Initiative. The Moonshot goal is to cut the cancer death rate by 50% over the next 25 years, and to increase early detection.”
During November, Pancreatic Cancer Awareness Month, Ms. Reynolds said the institute will introduce a YouTube podcast series: “Until There is a Cure,” where she will interview physicians, pancreatic cancer survivors and family members who have faced the trauma of caregiving.
“African American men have higher rates of pancreatic cancer than African American women, and African Americans as a cohort, have higher rates than White Americans. We’re beginning to explore data on Latinos and Asians,” Ms. Reynolds said. “We don’t yet know if there is a causal link between Type 2 diabetes and pancreatic cancer. We haven’t seen evidence of robust clinical trials to test that hypothesis, so there is a need to fund that research.”
“As a key part of our mission, the podcast series will feature discussions about pain management. Within the health care universe, there resides this pervasive myth that African Americans can tolerate greater pain than others. That ignorance often results in inadequate, improper, or simplistic interventions or dosages for pain, for example, that morphine is the most effective regimen.”
Ms. Reynolds had her own negative experience with morphine. “I did well using dilaudid as an alternative. Charles, zombie-like under morphine, was more alert with dilaudid as well. It doesn’t work for everyone, but it worked for him. But the point is for family members to learn how to become better advocates for loved ones. I know Charles would have done the same for me. He was the man who taught me love.”
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