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Metastatic melanoma faces challenge from new T cell therapy.

‘Super cells’ show promise in treating deadly skin cancer

by Bethany Hubbard
April 27, 2011

White blood cells with long lives and super memories proved to be key in a new treatment of advanced melanoma, researchers at Boston’s Dana-Farber Cancer Institute reported in Wednesday’s issue of Science Translational Medicine.

The new antitumor T cell therapy is a form of adoptive immunotherapy that trains T cells, a type of white blood cell, to specifically target tumors. In similar treatments T cells faded within a few days, and methods used to extend their lives had significant side effects. But, these specially engineered cells remained in the patients’ bloodstreams for over a year, according to the study.

“One of the things that we were interested in trying to do was expand these antitumor cells in the laboratory, and infuse them into patients, but also try to imbue them with the ability to survive a longer period of time,” said lead researcher Dr. Marcus Butler.

Researchers removed T cells from the blood of nine patients with advanced melanoma, a deadly skin cancer. In the lab, the cells were injected with specific molecules that tell them to recognize cancer, as well as given growth factors aimed at increasing their chances of survival. Patients then received infusions of these “super” T cells.

The patients were not given any other treatments, such as chemotherapy, during the trial.

Seven of the trial participants had more of the tumor-hunting cells present than what they had started with ten weeks after beginning the therapy. Three were deemed stable, one saw a reduction in the size of a pulmonary tumor, and one experienced a complete remission, researchers reported, adding that the patient is still cancer-free today, 25 months later.

Though he is pleased with the results, Butler said that every success must be taken with a grain of salt.

“Cancer is different in every patient,” he said.

Still, there is promise that combining the T cell infusions with other treatments may prove to be a successful cancer-fighting combination.

“A lot of people who are interested in adoptive therapy are interested in combining treatments,” Butler said.

This technique was used with five of the patients, whose diseases eventually progressed.

When given a recently FDA-approved drug called ipilimumab in tandem with T cell infusions, three of the patients’ tumors decreased in size, and two of the patients stabilized.

Ipilimumab improves T cell response and also blocks CTLA-4, which is a protein that sends an inhibitory signal to the immune system.

“We’re in an era where the details of how an antitumor immune response is regulated are becoming more and more clear – better defined,” said Dr. Thomas Gajewski, an immunotherapy expert at the University of Chicago Medical Center. “This has given many new opportunities for intervention to try and promote better immune-mediated control of cancer.”

He said that one of the reasons the field is excited about these methods is that there is currently very little that can be done once tumors have metastasized.

“Once the cancer has spread, there are very few therapies that are curative for most cancers,” he said.

But, if immunotherapy does work, there is hope for durable complete responses, and even remission, such as the one trial patient experienced.

The National Cancer Institute reported an estimated 68,130 new melanoma cases and 8,700 deaths from the disease in the U.S. in 2010.

Butler said his team plans to continue to study how T cell infusions can work with other therapy treatments.