For
more than a century, researchers were puzzled by the uncanny ability of
cancer cells to evade the immune system. They knew cancer cells were
grotesquely abnormal and should be killed by white blood cells. In the
laboratory, in Petri dishes, white blood cells could go on the attack
against cancer cells. Why, then, could cancers survive in the body?
The answer, when it finally came in
recent years, arrived with a bonus: a way to thwart a cancer’s strategy.
Researchers discovered that cancers wrap themselves in an invisible
protective shield. And they learned that they could break into that
shield with the right drugs.
When the immune system is free to
attack, cancers can shrink and stop growing or even disappear in lucky
patients with the best responses. It may not matter which type of cancer
a person has. What matters is letting the immune system do its job.
So far, the drugs have been tested and
found to help patients with melanoma, kidney and lung cancer. In
preliminary studies, they also appear to be effective in breast cancer,
ovarian cancer and cancers of the colon, stomach, head and neck, but not
the prostate.
It is still early, of course, and
questions remain. Why do only some patients respond to the new
immunotherapies? Can these responses be predicted? Once beaten back by
the immune system, how long do cancers remain at bay?
Still, researchers think they are seeing the start of a new era in cancer medicine.
“Amazing,” said Dr. Drew Pardoll, the
immunotherapy research director at Johns Hopkins School of Medicine.
This period will be viewed as an inflection point, he said, a moment in
medical history when everything changed.
“A game-changer,” said Dr. Renier J. Brentjens, a leukemia specialist at Memorial Sloan-Kettering Cancer Center.
“A watershed moment,” said his
colleague, Dr. Michel Sadelain. (Both say they have no financial
interests in the new drugs; Pardoll says he holds patents involving some
immunotherapy drugs, but not the ones mentioned in this article.)
Researchers and companies say they are
only beginning to explore the new immunotherapies and develop others to
attack cancers, like prostate, that seem to use different molecules to
evade immune attacks. They are at the earliest stages of combining
immunotherapies with other treatments in a bid to improve results.
“I want to be very careful that we do
not overhype and raise patients’ expectations so high that we can never
meet them,” said Dr. Alise Reicin, a vice president at Merck for
research and development.
But the companies have an incentive to
speed development of the drugs. They are expected to be expensive, and
the demand huge. Delays of even a few months mean a huge loss of
potential income.
Nils Lonberg, a senior vice president at
Bristol-Myers Squibb, notes that immunotherapy carries a huge advantage
over drugs that attack mutated genes. The latter approach all but
invites the cancer to escape, in the same way bacteria develop
resistance to antibiotics.
By contrast, immunotherapy drugs are
simply encouraging the immune system to do what it is meant to do; it is
not going to adapt to evade the drugs.
“We are hoping to set up a fair fight between the immune system and the cancer,” Lonberg said.
The story of the new cancer treatments
started with the discovery of how cancers evade attacks. It turned out
that they use the body’s own brakes, which normally shut down the immune
system after it has done its job killing virus-infected cells.
One braking system, for example, uses a
molecule, PD-1, on the surface of T-cells of the immune system. If a
target cell has molecules known as PD-L1 or PD-L2 on its surface, the
T-cell cannot attack it.
So some cancer cells drape themselves in
those molecules. The effect, when T-cells are near, is like turning off
a light switch. The T-cells just shut down.
Cancers that do not use PD-L1 or PD-L2
are thought to use other similar systems, just starting to be explored.
Body systems have a lot of redundancy to tamp down immune attacks. But
for now, the PD system showed researchers how cancer cells can evade
destruction.
New York Times News Service
No comments:
Post a Comment