Genes - cancer

'Gene therapy' works on 2 cancer patients

Treatment failed 15 others with melanoma
THE WASHINGTON POST and ASSOCIATED PRESS
September 1, 2006

WASHINGTON -- A team of researchers from the National Cancer
Institute yesterday reported they have successfully treated two
cancer patients using "gene therapy," the introduction of genes
into the human body for medical purposes.
Two men, both with the rapidly growing skin cancer melanoma, were
given immune system cells taken from their own blood and engineered
to attack their tumors. They are alive, with no evidence of cancer,
18 months later. Fifteen other patients who got the same treatment
died.
The report, published online by the journal Science, is the latest
result of a three-decade effort led by surgeon Steven Rosenberg to
find ways to manipulate the human immune system to fight cancer.
Neither Rosenberg nor others would describe the two patients as
"cured." At least five years would need to pass before such a
declaration would be considered. Cancer sometimes returns even after
that much time has lapsed.
"I'm cured for now," is how a grateful Mark Origer, 53, of
Watertown, Wis., put it after a checkup from NCI doctors this week.
"I know how fortunate I am to have gone through this and responded
to this. Not everybody's that lucky."
Gene therapy was once viewed as the great hope for treating, or even
curing, a long list of diseases. But tests of the concept since the
late 1980s have been overwhelmingly disappointing.
"I do consider this a proof of the principle that it can work,"
Rosenberg said yesterday. "I have every expectation that we can get
it to work better."
Response by others in the field was positive but not effusive.
"I think it is an important landmark to see some cancer patients
respond to a gene therapy - finally," said Patrick Hwu, a physician
and gene-therapy researcher at University of Texas M.D. Anderson
Cancer Center in Houston, who was not involved in the study. "I
think that clearly all of us want to do better than 2 out of 17."
Rosenberg has long led a tantalizing research field: how to harness
the body's immune system to fight cancer. White blood cells called
T-lymphocytes hunt down germs and other foreign tissue. But
cancerous cells look a lot like healthy cells, making it hard for
those T-cells to spot a problem.
By 2002, Rosenberg had made a breakthrough. He found small numbers
of cancer-fighting T-cells inside some patients with advanced
melanoma. He literally pulled those cells out of their blood, and
grew billions more of them in laboratory dishes, enough to have a
chance at overwhelming a tumor when they're pumped back into
patients. About half significantly improve after this so-called
?cell-transfer therapy."
But few melanoma patients make enough cancer-fighting T-cells
naturally for scientists to spot in their bloodstream. So Rosenberg
and colleagues set out to create those tumor fighters from scratch.
The scientists took normal lymphocytes out of 17 patients with
advanced melanoma. They infected those cells with a virus carrying
genes that create T-cell receptors, essentially homing devices for,
in this case, melanoma.
"We can take a normal cell from you or me or any patient and . . .
convert that cell into a cell that recognizes the cancer," Rosenberg
explained.
In 15 of the 17 patients who tried it, the newly armed cells took
root and grew at low levels for a few months. But only two saw their
tumors gradually fade away ? Origer and a 30-year-old whose T-cell
levels remained super-high for more than a year.
Rosenberg said he is awaiting Food and Drug Administration approval
to attempt the treatment on lung and breast cancer patients.



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