Novel immunotherapy for pancreatic cancer employed by Providence researchers featured in New England Journal of Medicine
It was back. Kathy Wilkes’ pancreatic cancer was back. Metastasized into her lungs. “I had one job, stay alive,” said Wilkes.
Wilkes’ efforts to stay alive – with a 72% reduction in the size of her tumors to date – are detailed in the article Neoantigen T-Cell Receptor-Gene Therapy in Pancreatic Cancer published this week in the New England Journal of Medicine. Rom Leidner, M.D., and Eric Tran, Ph.D., both with Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, devised and led Wilkes’ first-of-a-kind single patient clinical trial.
In search of an immunotherapy treatment
By 2019, Wilkes had fought her deadly pancreatic cancer with every conventional treatment, an extensive surgery, radiation, and multiple rounds of chemotherapy. The cancer evaded all of these treatments and the nodules in her lungs continued to grow.
“I knew I did not want to do chemo again,” said 72-year-old Wilkes. “It would not save my life, it might prolong it, but it would not be the quality of life I would want. So, I researched immunotherapy.”
The Florida resident found a 2016 New England Journal of Medicine article authored by Dr. Tran that described a patient with metastatic colorectal cancer that was successfully treated with adoptive cell therapy during his time as the National Institutes of Health.
She needed to talk with Dr. Tran.
“He wasn’t at the NIH anymore,” said Wilkes. “I found him on the other side of the country, at Providence Cancer Institute in Portland, Ore. I placed a call and left a message. I was elated when he called me back.”
Dr. Tran had joined Providence in 2017 to develop and lead the Adoptive Cell Therapy Laboratory at the Earle A. Chiles Research Institute, which is the research arm of Providence Cancer Institute.
Dr. Eric Tran, assistant member, Adoptive Cell Therapy Laboratory, Earle A. Chiles Research Institute, a division of Providence Cancer Institute
He and Dr. Leidner reviewed the details of Wilkes’ medical history, complete with cancer mutations identified through genetic testing, and applied for expedited approval from the Food and Drug Administration for a single-patient adoptive cell therapy clinical trial.
Dr. Rom Leidner, co-medical director, Providence Head and Neck Cancer Program, and associate member,
Earle A. Chiles Research Institute, a division of Providence Cancer Institute
The trial involved getting a blood sample from Wilkes, isolating and invigorating her T cells in the lab, reprogramming them to target one of Wilkes’ cancer mutations, multiplying them to 16 billion, and infusing them back into Wilkes on June 14, 2021.
Thirty days later, a scan showed the tumors in her lungs had shrunk 62 percent. Six months out from that infusion, the tumors had stabilized at 72 percent reduction of their original size.
“I had hope and I had the belief that I was going to live,” said Wilkes. “The best call I ever made was to Dr. Tran.”
“There really are no effective treatments for metastatic pancreatic cancer,” said Dr. Tran, assistant member, Adoptive Cell Therapy Lab, Earle A. Chiles Research Institute, a division of Providence Cancer Institute. “The fact that a single infusion of reprogrammed T cells could cause Kathy’s metastatic pancreatic cancer to shrink for over six months makes me optimistic that we are on the right track. Now we have to make this therapy more potent and work for more patients.”
“We are at the doorstep of what may be a breakthrough "living drug," said Dr. Leidner, co-medical director, Providence Head and Neck Cancer Program and associate member, Earle A. Chiles Research Institute, a division of Providence Cancer Institute. “An enormous body of research led up to this accomplishment and years of work lie ahead. There is no better place than the Earle A. Chiles Research Institute for the visionary and indefatigable commitment needed to develop this kind of groundbreaking cancer treatment.”
The clinical trial designed for Wilkes was built on the findings of the 2016 New England Journal of Medicine article that Dr. Tran authored while at the NIH. In that study, Dr. Tran found tumor-infiltrating T cells that targeted a common cancer mutation in a patient with metastatic colorectal cancer. These mutation-reactive T cells were expanded in the lab and then over 100 billion of them were infused into the patient, which led to regression of her metastatic disease.
Because Wilkes’ tumor contained the same mutation as the patient described in the 2016 study, and another genetic factor (called HLA) matched, Dr. Tran’s team was able to use the mutation-reactive T-cell therapy for Wilkes. In this approach, the mutation-reactive T-cell receptors were genetically inserted into Wilkes’ T cells to reprogram them to attack Wilkes’ cancer.
In both approaches, the treatment was highly personalized.
New clinical trial for people with metastatic cancers
Drs. Tran and Leidner have now opened a larger phase 1 adoptive cell therapy clinical trial for patients with epithelial cancers, which includes a broad array of the most common cancer types, responsible for 85 percent of annual cancer deaths.
In this trial, like Wilkes’ treatment, T cells from patients are genetically engineered to express a receptor that redirects the T cells to attack a specific cancer mutation. Patients are then treated with these gene engineered T cells along with two additional immunotherapy agents that should further enhance the activity and efficacy of the transferred T cells.
Wilkes is honored to have helped advance Dr. Tran’s research.
“I hate to say cancer was a good thing that happened to me, because nobody thinks that cancer is good,” said Wilkes. “But actually, it kind of was because it gave me a purpose.
“Everyone goes through life asking, ‘what’s your purpose?’ – mine turned out to be surviving cancer and providing hope to other people.”
Philanthropy supports research
The published research and newly opened trial is the continuation of Dr. Tran’s goal of developing new and more effective T cell-based immunotherapies. Philanthropy is a critical factor in funding new cancer therapies, with generous donors giving more than $6 million five years ago to launch Dr. Tran’s research. In 2021, donors gave $10 million to Providence Cancer Institute, including $8.6 million to fund research.
Providence Cancer Institute is one of a limited number of centers nationwide that have the expertise to generate experimental adoptive-cell therapy products to treat patients with cancer.