An Irish American woman with advanced colon cancer has seen a remarkable recovery after a new treatment has left her cancer free. Her case may lead to new options for hundreds of thousands of people with colon or pancreatic cancer.
Celine Ryan, a 50-year-old engineer, database programmer and mother of five, from Rochester Hills, MI had colon cancer that spread to her lungs despite surgery, chemotherapy and radiation. After being treated with cells from her own immune system, she is now cancer-free, although she is not considered cured.
The treatment, a form of immunotherapy in which a patient’s immune system is enlisted to fight disease, is revolutionizing cancer treatment, the New York Times reports.
Ryan’s treatment was the first to successfully target a common cancer mutation that is so resistant that scientists have described it as “undruggable.”
An article about Ryan's case, from a team led by Dr. Steven A. Rosenberg, chief of surgery at the National Cancer Institute, has been published in The New England Journal of Medicine.
“It has huge implications,” says Dr. Carl H. June, from the University of Pennsylvania. June was not part of the study, but wrote an editorial accompanying it in the journal.
He told the New York Times that the research was the first successful targeting of a defect in a gene called KRAS, and is important because mutations in the gene are so common.
“Every single pancreatic cancer patient has KRAS,” Dr. June said, adding that the pharmaceutical industry has spent billions trying unsuccessfully to target the gene.
He says the bigger question of the study is whether Ryan’s case is “one in a million, or something that can be replicated and built upon?”
The research involves cancer-fighting immune cells called tumor-infiltrating lymphocytes, or TILs, white blood cells that swarm around tumors, an indication that the immune system is trying to attack the cancer.
Dr. Rosenberg has been studying TILs for years, hoping to enhance their ability to fight the disease and use them as a treatment.
The latest discover might not have been made had it not been for Ryan’s persistence. She was twice told 'No' for the clinical trial because, she was told, she did not have a tumor big enough to yield TILS. She refused to give up and was finally allowed to join the study in March 2015.
An attempt to treat another patient with tumors much like Ryan’s had been unsuccessful because the researchers could not produce enough highly targeted TILs. However, Ryan’s tissue “turned out to be a medical gold mine.”
The New York Times reports: “She had a KRAS mutation and her TILs included killer T-cells that locked onto the mutation like guided missiles.
“Her T-cells were able to recognize the mutation because she has an uncommon tissue type, which is a genetically determined trait. As a result, she carries a certain protein on the surface of her cells that plays an essential role in displaying the KRAS mutation so that cancer-killing cells can find it and attack.
“Best of all, from a scientific standpoint, was that Ms. Ryan’s KRAS mutation is shared by many other patients with colon and pancreatic cancers. Those who share her tissue type may also be good candidates for treatment with TILs.”
Ryan had seven tumors in her lungs. After treatment six of the tumors shrank and then disappeared over the next nine months. The seventh shrank initially, but then progressed. Surgeons took out the lower lobe of her left lung to remove it.
Tests revealed why the excised tumor had resisted treatment. The tumor had mutated and no longer carried the tissue-type marker that had enabled the T-cells to attack it.
Dr. Drew M. Pardoll, the director of the Bloomberg-Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins University School of Medicine, says that this ability to escape the T-cells does reveal a potential weak spot in the approach of targeting a single mutation.
Cancer is “versatile,” he said. “The tumor always seems to come up with a workaround,” but despite this the research was “a real and solid step forward.”
“This is truly exciting,” Axel Grothey, a Mayo Clinic oncologist, told the Wall Street Journal. “At this point in time I consider the presented data as an intriguing proof of principle that cellular immune therapy can be used to target cancer cells with specific molecular alterations. That alone is important and could represent a game-changer in the future.”
“This is really important,” said Leonard Saltz, chief of gastrointestinal oncology at the Memorial Sloan Kettering Cancer Center in New York. “It isn’t changing treatment today, but it may change it tomorrow.” He expressed caution because this is just one case, but said, “This is a terrific translation of elegant science into a real benefit for this patient, so in that respect it’s very exciting.”
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