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Immune Cells Used to
Stop Severe Cancer
New Approach Brings Success to an Old Idea
By
David Brown, Washington Post,
September 20, 2002,
www.washingtonpost.com
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A
research team at the National Cancer Institute has successfully
treated several cases of advanced and usually fatal cancer with
immune system cells taken from the patients, grown in large
numbers and given back to them.
The
treatment is one of many strategies scientists are using to try
to harness the human immune system's capacity to produce rare
cells capable of hunting down and attacking tumors.
The
research also marks the first success in a decade for a
once-highly touted strategy conceived by Steven A. Rosenberg, a
cancer institute surgeon and one of the founders of "immunotherapy."
His experiments in the late 1980s, first with mice and then with
humans, were viewed by some as the path to the elusive "cure for
cancer." Their clinical results, however, were disappointing in
almost all cases.
The
new strategy worked only half the time and has been tried only
in the skin cancer known as melanoma, but the results suggest it
may be applicable to other malignancies.
"As a
proof of principle, he's hit a home run," Robert A. Figlin, an
oncologist and immunotherapist at the University of California
at Los Angeles School of Medicine, said of Rosenberg's findings.
They are reported today in Science Express, the online site for
the journal Science.Most of the steps of the therapy had been
tried before, but "what's new here is putting all the pieces
together to get a more successful outcome," said Richard Childs,
a physician at the National Heart, Lung and Blood Institute who
has tried immunotherapy, with some success, in kidney cancer
patients.
The
treatment produced several dramatic recoveries, Rosenberg
reported yesterday at a meeting of science writers organized by
the American Medical Association. One teenage boy had a
"volley-ball-size tumor" in his pelvic cavity that caused so
much pain he required around-the-clock treatment with narcotic
painkillers. It disappeared with immunotherapy, Rosenberg said.
Melanoma, which is a cancer of the skin's pigment-producing
cells, can be cured by surgery, but not chemotherapy. Once it
has spread to distant organs, few, if any, people survive for a
long time.
The
National Cancer Institute team treated 13 patients with advanced
forms of the cancer. They had exhausted all other therapies,
including at least one designed to stimulate their immune
systems. After the new treatment, six responded with what
appears to be total disappearance of the tumors. Four had
partial responses that are not expected to last (although one
patient's disease has been stable for a year). Three had no
response and have died.
Rosenberg's strategy has always been to exploit the existence of
immune system cells that can be found buried deep in cancerous
tumors fighting a valiant, but almost always futile, battle
against the rapidly dividing cells.
In the
1980s, he and his colleagues isolated these "tumor-infiltrating
lymphocytes" (TIL), grew them up in culture dishes outside the
body and reinfused them into the bloodstream. Although they
appeared to retain their anti-cancer properties, they didn't
survive in the body long enough to make a practical difference.
In
their most recent strategy, the researchers isolated TIL from
multiple samples of each patient's tumor and grew them in the
laboratory. As many as 50 different samples from each patient
were tested against the person's cancer cells. The samples that
killed the most cancer cells were selected for reinfusion into
the bloodstream.
Before
that was done, the patients underwent chemotherapy to
temporarily wipe out their immune systems and "make room" for
the incoming TIL. After the reinfusion, each person also
received numerous doses of interleukin 2, an immune system
hormone previously shown to stimulate anti-tumor activity.
Unlike
in previous experiments, large quantities of TIL were found in
the bloodstreams of several of the patients. It was clear that
in some patients, the cells not only survived, but proliferated.
For
example, in one patient whose tumor disappeared, 97 percent of
bloodstream lymphocytes were anti-cancer a week after the
infusion. In another, 63 percent were anti-cancer. In those two
patients, tumor-infiltrating lymphocytes were still detectable
four months later.
A main
reason for the greater success of this treatment, several
experts said, is that a mixture of lymphocytes -- helper and
killer cells -- were used. Previously, many researchers,
including Rosenberg, had used only killer cells. This meant the
new infusions were a melange of cells with different
characteristics and extremely complicated relationships with
each other.
In
four patients, the TIL attackers were so active they killed some
normal pigment-producing cells, creating white areas of skin, a
condition called vitiligo. This suggested that side effects
could pose a problem in treatment of other cancers.
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