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Sunday, 03-September-2006
LOS ANGELES, (Xinhua) - Normal immune cells have become specialized tumor fighters after being genetically engineered, and for the first time, persist in the body and shrink large tumors in humans, scientists reported on Thursday.
The technique, tested in 17 patients with advanced melanoma with two cures, will pave the way for a new approach to fight cancer by boosting the body's own immune system instead of relying on toxic chemotherapy and radiation treatments to kill deadly tumors, said the researchers at the U.S. National Cancer Institute.
The study was published in the Aug. 31 edition of the online version of the journal Science.
The finding "represents the first time that gene manipulations have been shown to cause tumor regression in humans," said Steven Rosenberg, who led the study.
The researchers focused specifically on T cells, a special type of immune cell that can recognize and attack "foreign" cells such as those found in tumors.
In their earlier experiments, the researchers removed tumor-fighting T cells from melanoma patients and multiplied these cells in the laboratory. After using chemotherapy to clear out a patient's old T cells, the researchers repopulated the patients' immune systems with these new fighters.
But some people with melanoma do not have these tumor-fighting T cells, and in other types of cancer it is difficult to identify T cells that attack tumors, the researchers said, so they came up with a way to create these types of T cells from scratch.
T cells carry a receptor protein on their surface that recognizes specific molecules called antigens on tumor cells. The receptor's genetic makeup determines the antigen types that the T cell can recognize, so that some cells contain genes that make a Tcell receptor that homes in on melanoma cells, while other cells contain genes that make a T cell receptor that recognizes breast or lung cancer cells.
The researchers created tumor fighters by removing normal T cells from people with advanced metastatic melanoma, genetically engineering these normal cells to carry the receptor that recognizes melanoma cells and returning these "re-armed" cells to rebuild the patients' immune systems.
The newly engineered T cells showed signs of persistence in 15 of the patients in the study, making up at least 10 percent of their circulating T cells for at least two months after treatment.
In two people, tumors shrunk noticeably with the treatment, and the new T cell levels were higher.
Devising new ways to insert the receptor genes in the T cells, usually encoded in a retrovirus, has been one of the most challenging aspects of the treatment, Rosenberg said.
"It's a lot of sophisticated molecular biology and most of our work is going into designing retroviruses, putting genes into cells efficiently and getting them expressed."
The researchers said they were now searching for ways to fine-tune the treatment so that greater numbers of the engineered T cells will survive and continue expressing their new receptor genes, since their expression does seem to wane over time.
So far, the therapy has only been used in this small group of melanoma patients, but Rosenberg said his team had demonstrated ways to engineer similar immune cells in the laboratory that would attack more common tumors such as breast, lung and liver cancers. Enditem
Editor: Lin Li

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