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New Therapies Offer Insight Into Battling Deadly Melanomas
Date:1/31/2011

By Amanda Gardner
HealthDay Reporter

MONDAY, Jan. 31 (HealthDay News) -- Two new studies report some success in treating a particularly stubborn form of cancer: melanoma, a deadly malignancy that first appears in the skin before frequently spreading to other parts of the body.

The first study, appearing in the Jan. 31 issue of the Journal of Clinical Oncology, used genetically engineered immune cells from the patient to fight off the cancer cells.

The second study, appearing in this week's issue of the Proceedings of the National Academy of Sciences, targeted a subgroup of cancer cells thought to be primarily responsible for metastasis -- the spread of cancer.

The technique used in the first study, which included 17 patients, is called "adoptive immunotherapy."

Basic immunotherapy involves "removing [immune] cells from the patients, growing them to large numbers, then giving them back," explained study senior author Dr. Steven A. Rosenberg, chief of surgery at the U.S. National Cancer Institute.

The researchers went one step further by modifying the cells to recognize and bind to a specific protein on cancer cells, NY-ESO-1.

"We genetically engineered them to recognize the cancer," said Rosenberg. "Basically we created a new drug for every patient, using their own cells to treat them."

Forty-five percent of melanoma patients in the study responded to the therapy, as did about two-thirds of patients with a rare soft-tissue cancer known as synovial cell sarcoma, which attacks muscle, fat, blood tissue and tissue lining the joints. Two of the 11 melanoma patients saw their cancer disappear for more than a year.

The synovial cell sarcoma findings were significant, said Rosenberg, because "this is the first time we've [successfully] used gene therapy for a solid cancer other than melanoma."

Also, the NY-ESO-1 antigen is found in many other cancers, including breast, prostate, esophageal, lung and ovarian malignancies, meaning the treatment might work in those patients as well.

But, so far, the therapy is experimental and has only been shown to work in a few patients, albeit with minimal side effects.

"It's a very labor-intensive procedure," said Dr. Warren Chow, associate professor of medical oncology at City of Hope Cancer Center in Duarte, Calif. "It's not going to be something that a lot of people are going to be able to do [right away]."

The technique used in the second study was similar to that demonstrated in the Rosenberg study.

Here, the researchers genetically engineered human immune cells to target two cancer-related proteins on cancer cells, then injected these cells into mice with human melanomas.

The proteins seem to belong to a subgroup of tumor cells that are somehow more significant in making melanoma more lethal.

"They're targeting the cancer stem cell, which is becoming very popular now," Chow said.

Most of the tumors shrank and stayed that way for up to 36 weeks. The method still needs to be tested in humans. And studies that start with animals often fail to produce desired results in people.

The immune treatments certainly make sense, said Dr. Edibaldo Silva, an associate professor of surgical oncology at the University of Nebraska Medical Center in Omaha.

And, in a way, any news is good news for a cancer like melanoma that has such a dismal prognosis. Interferon, which has been used for 20 years, has awful side effects even though it prolongs life.

"You live one year longer, but you're miserable from side effects," Silva said. "The medical community has been disheartened."

More information

The U.S. National Cancer Institute has more on metastatic cancer.

SOURCES: Steven A. Rosenberg, M.D., Ph.D., chief, surgery, U.S. National Cancer Institute; Edibaldo Silva, M.D., Ph.D., associate professor, surgical oncology, University of Nebraska Medical Center, Omaha; Warren Chow, M.D., associate professor, medical oncology, City of Hope Cancer Center, Duarte, Calif.; Jan. 31, 2011, Journal of Clinical Oncology; Jan. 31-Feb. 5, 2011, Proceedings of the National Academy of Sciences


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