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Engineering a Cure: Genetically modified cells fight cancer

Christen Brownlee

By inserting a gene into normal immune cells isolated from melanoma patients, scientists have turned the cells into cancer fighters. This new technique represents the first use of gene therapy to treat cancer, the researchers say.

In the past several years, scientists have been modestly successful in treating a few cancers using a method called adoptive cell transfer. This technique relies on the natural ability of certain immune cells called T cells or lymphocytes to recognize and kill cancer cells in some patients.

In this method, researchers first isolate a patient's most aggressive tumor-killing T cells and multiply them in the lab. Doctors destroy the patient's remaining T cells and replace them with the anticancer versions. If all goes well, these cells home in on tumors and kill them.

However, adoptive cell transfer isn't a viable treatment for the majority of people with cancer, explains Steven A. Rosenberg of the National Cancer Institute in Bethesda, Md. For example, only half of melanoma patients seem to have these specialized tumor-killing T cells, and the cells that target other types of cancers such as breast, lung, and liver cancer are "very difficult to find" in people with those diseases, he says.

Seeking to broaden the technique's reach to more cancer patients, Rosenberg and his colleagues combined it with a type of gene therapy. The researchers worked with 17 people with advanced melanoma that other treatments had failed to control.

Rosenberg's team removed some T cells from each person's blood. Then, instead of looking for cells that specifically target melanoma, the scientists infected the cells with a virus that caused them to express a protein called MART-1 on their surfaces. This protein is known to make T cells recognize and kill melanoma tumors.

The researchers infused the modified cells back into their original owners. Over the next several months, two of the patients had dramatic regressions of their tumors and are now considered diseasefree. Although tumors didn't regress in the remaining 15 patients, the scientists found that at least 10 percent of the cancer-fighting cells survived and continued to circulate in these patients' bloodstreams.

Rosenberg says that he and his team aren't sure why the anticancer responses differed among the patients. However, he says that the fact that the cancer-fighting cells persisted in all the patients is "very encouraging."

"It's a proof of principle that you can take normal cells, engineer them, and make them recognize and destroy cancer. Once you know it's possible, you have the potential to improve upon it," Rosenberg says.

He and his team are currently working on inserting genes into T cells that prompt more-aggressive anti-melanoma responses or responses to other common types of cancer.

The findings, published in an upcoming Science, could eventually make adoptive cell transfer part of the standard therapy for many types of cancer, says New York University cancer immunologist Michelle Krogsgaard.

"The problem with adoptive cell transfer is it's a really good idea but it hasn't been that successful," she says. The new paper "opens up a lot of possibilities ... to manipulate T cells for transfers that you couldn't do before."

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References:

Morgan, R.A. … and S.A. Rosenberg. In press. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. Abstract.

Further Readings:

Dudley, M.E. … and S.A. Rosenberg. 2002. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298(Oct. 25):850–854. Abstract.

Rosenberg, S.A. 1999. A new era for cancer immunotherapy based on the genes that encode cancer antigens. Immunity 10(March):281–287. Abstract.

Sources:

Renier J. Brentjens
Memorial Sloan-Kettering Cancer Center
1275 York Avenue
New York, NY 10021

Michelle Krogsgaard
SRB 13th Floor 1311
522 First Avenue
New York University Medical Center
New York, NY 10016

Steven A. Rosenberg
Surgery Branch
Center for Cancer Research
National Cancer Institute
National Institutes of Health
10 Center Drive
Bethesda, MD 20892

Ton Schumacher
Department of Immunology
Netherlands Cancer Institute
Plesmanlaan 121
Netherlands


From Science News, Volume 170, No. 10, September 2, 2006, p. 147.