New Method of Gene Therapy for Treating Advanced Melanoma
Melanoma accounts for only about 4% of skin cancer cases, but it’s the most
serious and aggressive type of skin cancer. An estimated 62,190 new cases will
be diagnosed in the U.S. this year and approximately 7,910 people will die of
the disease. A team of researchers at NIH’s National Cancer Institute (NCI) have
now genetically engineered patients’ own white blood cells to recognize and attack
advanced melanomas.
This is the first time that gene therapy has been used successfully to treat cancer.
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Researchers have previously shown that lymphocytes — white blood cells from the
immune system — can be used to treat melanoma. Lymphocytes are removed from patients
with advanced melanoma and the most aggressive tumor-killing cells isolated and
multiplied in the lab. These are then reintroduced into patients who’ve had their
remaining lymphocytes depleted. However, this method only works for people whose
lymphocytes already recognize tumors as abnormal and it’s not effective for other
cancers.
NCI researchers led by Dr. Steven A. Rosenberg sought an effective way to convert
normal lymphocytes into cancer-fighting cells. They drew a small sample of blood
that contained normal lymphocytes and infected the cells with a retrovirus in the
laboratory. This retrovirus delivers genes encoding proteins called T
cell receptors (TCRs). When the genes are turned on, they cause the lymphocytes
to make TCRs, which then decorate their outer surfaces. The TCRs act as homing
devices for the cells, recognizing and binding certain molecules found on the surface
of tumors. The lymphocytes then destroy the cancer cells they’re attached to.
In the online edition of the journal Science on August 31, 2006, the
researchers describe how these engineered lymphocytes were infused into 17 patients
with advanced metastatic melanoma that had not responded to previous treatments.
The first group of three patients showed no delay in the progression of their
disease. The researchers then returned to the lab to improve the treatment of
lymphocytes so that they could be administered in their most active growth phase.
All the patients who received the improved treatments still had at least 10%
of their lymphocytes making TCR for more than two months. Two of the patients
experienced cancer regression and remained disease-free over a year and a half
after treatment. There were no toxic side effects attributed to the genetically
modified cells.
Now that the researchers have proved this strategy can be successful, they’re
testing several methods to improve its effectiveness. In addition, Rosenberg
said, “We have now expressed other lymphocyte receptors that recognize breast,
lung and other cancers.”
“These results represent the first time gene therapy has been used successfully
to treat cancer,” NIH Director Dr. Elias A. Zerhouni said. “We hope it will be
applicable not only to melanoma, but also for a broad range of common cancers,
such as breast and lung cancer.”
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