WASHINGTON - Government
scientists turned regular blood cells into tumor attackers that wiped out all
signs of cancer in two men with advanced melanoma. The striking finding,
unveiled Thursday, marks an important step in the quest for gene therapy for
cancer.
But the genetically altered cells didn't help 15 other melanoma victims. So
scientists are trying to strengthen the shots.
Still, the National Cancer Institute called its experiment the first real
success in cancer gene therapy because it fought cancer's worst stage, when it
has spread through the body, unlike earlier attempts that targeted single
tumors.
And the government hopes to soon begin testing the gene therapy in small
numbers of patients dying from more common cancers, such as advanced breast or
colon cancer.
The hope is that one day, such treatment might provide long-lasting tumor
suppression.
"It's not like chemotherapy or radiation, where as soon as you're done,
you're done," said lead researcher Dr. Steven Rosenberg, the NCI's surgery
chief. "We're giving living cells which continue to grow and function in the
body."
The first two successful patients appear melanoma-free almost two years after
infusions of tumor fighters made from their own blood. Doctors can't predict how
the men will fare long-term. Melanoma, the most aggressive skin cancer and
killer of almost 8,000 Americans a year, is notorious for returning years after
patients think they've subdued it.
"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."
Cancer specialists praised the work, published Thursday by the journal
Science, but warned that years of additional research are needed.
"Clearly this is a first step," cautioned Dr. Len Lichtenfeld of the American
Cancer Society. "We have to be very cautious about not raising hopes too much."
But, "it is exciting," he added. "It certainly is a proof of concept that
this approach will work."
NCI's 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, and T-cells that attack other cancers
are virtually impossible to find. So Rosenberg and colleagues set out to create
those tumor fighters from scratch.
The scientists took normal lymphocytes ones that don't recognize cancer out
of 17 patients with advanced melanoma who had exhausted their treatment options.
They infected those cells with a virus carrying genes that create T-cell
receptors, essentially homing devices for, in this case, melanoma. (Different
genes create receptors for other cancers.)
"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
over a year.
Why did the genetically altered cells flourish in only two people?
"That's the critical question," said Dr. Patrick Hwu, melanoma chairman at
the University of Texas M.D. Anderson Cancer Center, who once worked with the
NCI team.
Picking the right lymphocyte to genetically alter isn't easy - there are many
different kinds or perhaps more precise T-cell receptors were needed, Hwu
suggested.
But "these are all solvable issues," he stressed, calling the study "one of
the first documented, effective cases of cancer gene therapy working."
