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12/07/16

Cancer Breakthrough Aids One Patient, Raises Hopes for Many

Researchers use a woman’s immune cells for new therapy to reverse her metastatic colon cancer By THOMAS M. BURTON

BETHESDA, Md.—National Cancer Institute researchers have produced an immune-cell therapy that for the first time successfully targeted a genetic mutation involved in causing tens of thousands of gastrointestinal cancers.

The research, published in the New England Journal of Medicine on Wednesday, focused on only one patient whose metastatic colon cancer was completely reversed. But that patient’s unusual story may hold promise for many others, doctors said. The therapy targets a gene mutation estimated to drive more than 50,000 new cases of GI cancers in the U.S. each year, including about 90% of often-lethal pancreatic cancers and 45% of all colorectal cancers.

The NCI laboratory is headed by famed immune-therapy researcher Steven A. Rosenberg, the chief of surgery at the cancer institute. He has previously published landmark findings showing that immune therapy has effectively treated many patients with metastatic melanoma, as well as those with blood cancers such as leukemia and lymphoma. The technique also proved successful in a bile-duct cancer case reported in 2014. NCI is part of the National Institutes of Health, which is based here.

Targeting the commonly-occurring family of cancer-driving genes known collectively as RAS has been a kind of Holy Grail in oncology. Mutations in the subset of RAS genes known as KRAS are believed to be a driving force in most pancreatic cancers, which have a bleak survival rate, and in nearly half of colorectal cancers, the No. 2 cancer killer in the U.S. after lung cancer. In this case, the targeted mutated gene is known as KRAS G12D and is the most common of the KRAS gene mutations.

“We report the regression of metastatic colon cancer,” wrote the researchers, headed by Dr. Rosenberg and postdoctoral fellow Dr. Eric Tran. The researchers calculated that tens of thousands of patients annually could potentially be eligible for this treatment.

Dr. Rosenberg said that while the therapy depends on each patient’s own immune cells, it is potentially transferrable to many other patients because of receptors in the patient’s immune cells that grab onto the cancer. These anti-KRAS receptors can be widely used as a treatment, he said.

“This is truly exciting,” said Axel Grothey, a Mayo Clinic oncologist. “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.”

Efforts to try to produce drugs or vaccines that would be effective against tumors with the RAS mutations have been largely unsuccessful for about 25 years.

“Metastatic gastrointestinal cancers” with mutant KRAS genes “have one of the most dismal outcomes of all solid tumors and present an unsolved problem in cancer medicine,” said Carl H. June, a University of Pennsylvania immune-therapy specialist. “Despite considerable effort, researchers have not been able to develop” drugs that “have acceptable safety and clinical activity.”

The therapy involves taking the patient’s own cancer-attacking immune cells, called tumor-infiltrating lymphocytes, from nodules in her lungs. These cells were concentrated in flasks and incubators in the laboratory. A few thousand were initially taken from tumors and grown to about 148 billion carefully-selected cells infused back into the patient.

The person whose story is told in the published research is identified only as Patient 4095. Her name is Celine Ryan, a 50-year-old mother of five in Rochester Hills, Mich., who home-schools her children and counsels cancer patients.

Mrs. Ryan was operated on for colon cancer in September 2013, followed by chemotherapy and radiation. She believed the cancer was gone until imaging and a biopsy in late 2014 showed tumors in her lungs. Her doctors suggested more chemo, but instead she did her own research and learned about Dr. Rosenberg.

By April last year, doctors at the National Cancer Institute had harvested her immune cells, grown them in the lab and by July administered them back to Mrs. Ryan. All her seven lung tumors, step by step, disappeared—save one. That one had found a way to evade the immune-cell treatment, and has since been surgically removed. She now has been disease-free for eight months.

“Since all cancers contain mutations,” said Dr. Rosenberg, “using a patient’s own immune cells to target these mutations represents a personalized immunotherapy approach potentially applicable to many cancer types.”


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Source: http://www.wsj.com/articles/cancer-breakthrough-aids-one-patient-raises-hopes-for-many-1481148000