Home' Trinidad and Tobago Guardian : June 22nd 2017 Contents tobagotoday.co.tt June 21 - 2017
TURNING BLOOD INTO LIVING DRUGS
SEATTLE (AP) -- Ken Shefveland's body
was swollen with cancer, treatment after
treatment failing until doctors gambled on
a radical approach: They removed some of
his immune cells, engineered them into
cancer assassins and unleashed them into
Immune therapy is the hottest trend in
cancer care and this is its next frontier -
creating "living drugs" that grow inside the
body into an army that seeks and destroys
Looking in the mirror, Shefveland saw
"the cancer was just melting away." A month
later doctors at the Fred Hutchinson Cancer
Research Center couldn't find any signs of
lymphoma in the Vancouver, Washington,
"Today I find out I'm in full remission -
how wonderful is that?" said Shefveland
with a wide grin, giving his physician a quick
This experimental therapy marks an entire-
ly new way to treat cancer - if scientists can
make it work, safely. Early-stage studies are
stirring hope as one-time infusions of super-
charged immune cells help a remarkable
number of patients with intractable leukemia
"It shows the unbelievable power of your
immune system," said Dr. David Maloney,
Fred Hutch's medical director for cellular
immunotherapy who treated Shefveland with
a type called CAR-T cells.
"We're talking, really, patients who have
no other options, and we're seeing tumors
and leukemias disappear over weeks," added
immunotherapy scientific director Dr. Stan-
ley Riddell. But, "there's still lots to learn."
T cells are key immune system soldiers.
But cancer can be hard for them to spot,
and can put the brakes on an immune attack.
Today's popular immunotherapy drugs called
"checkpoint inhibitors" release one brake so
nearby T cells can strike. The new cellular
immunotherapy approach aims to be more
potent: Give patients stronger T cells to begin
Currently available only in studies at major
cancer centers, the first CAR-T cell therapies
for a few blood cancers could hit the market
later this year. The Food and Drug Admin-
istration is evaluating one version developed
by the University of Pennsylvania and licensed
to Novartis, and another created by the
National Cancer Institute and licensed to
CAR-T therapy "feels very much like it's
ready for prime time" for advanced blood
cancers, said Dr. Nick Haining of the
Dana-Farber Cancer Institute and Broad
Institute of MIT and Harvard, who isn't
involved in the development.
Now scientists are tackling a tougher next
step, what Haining calls "the acid test":
Making T cells target far more common
cancers - solid tumors like lung, breast or
brain cancer. Cancer kills about 600,000
Americans a year, including nearly 45,000
from leukemia and lymphoma.
"There's a desperate need," said NCI
immunotherapy pioneer Dr. Steven Rosen-
berg, pointing to queries from hundreds of
patients for studies that accept only a few.
For all the excitement, there are formida-
Scientists still are unraveling why these
living cancer drugs work for some people
and not others.
Doctors must learn to manage potentially
life-threatening side effects from an over-
stimulated immune system. Also concerning
is a small number of deaths from brain swell-
ing, an unexplained complication that forced
another company, Juno Therapeutics, to halt
development of one CAR-T in its pipeline;
Kite recently reported a death, too.
And, made from scratch for every patient
using their own blood, this is one of the
most customized therapies ever and could
cost hundreds of thousands of dollars.
"It's a Model A Ford and we need a Lam-
borghini," said CAR-T researcher Dr. Renier
Brentjens of New York's Memorial Sloan
Kettering Cancer Center, which, like Hutch,
has a partnership with Juno.
In Seattle, Fred Hutch offered a behind-
the-scenes peek at research underway to
tackle those challenges. At a recently opened
immunotherapy clinic, scientists are taking
newly designed T cells from the lab to the
patient and back again to tease out what
"We can essentially make a cell do things
it wasn't programmed to do naturally,"
explained immunology chief Dr. Philip Green-
berg. "Your imagination can run wild with
how you can engineer cells to function bet-
TWO LONG WEEKS TO BREW A DOSE
The first step is much like donating blood.
When leukemia patient Claude Bannick
entered a Hutch CAR-T study in 2014, nurs-
es hooked him to a machine that filtered out
his white blood cells, including the T cells.
Technicians raced his bag of cells to a
factory-like facility that's kept so sterile they
must pull on germ-deflecting suits, booties
and masks just to enter. Then came 14 days
of wait and worry, as his cells were repro-
Bannick, 67, says he "was almost dead."
Chemotherapy, experimental drugs, even a
bone marrow transplant had failed, and "I
was willing to try anything."
GENETICALLY ENGINEERING CELLS
The goal: Arm T cells with an artificial
receptor, a tracking system that can zero in
on identifying markers of cancer cells, known
as antigens. For many leukemias and lym-
phomas, that's an antigen named CD19.
Every research group has its own recipe
but generally, scientists infect T cells with
an inactive virus carrying genetic instructions
to grow the desired "chimeric antigen recep-
tor." That CAR will bind to its target cancer
cells and rev up for attack.
Millions of copies of engineered cells are
grown in incubators, Hutch technicians pull-
ing out precious batches to monitor if they're
ready for waiting patients.
If they work, those cells will keep multi-
plying in the body. If they don't, the doctors
send blood and other samples back to
researchers like Riddell to figure out why.
WHAT'S THE DATA?
Small, early studies in the U.S. made head-
lines as 60 percent to 90 percent of patients
trying CAR-Ts as a last resort for leukemia
or lymphoma saw their cancer rapidly
decrease or even become undetectable. Last
week, Chinese researchers reported similar
early findings as 33 of 35 patients with anoth-
er blood cancer, multiple myeloma, reached
some degree of remission within two months.
Too few people have been studied so far
to know how long such responses will last.
A recent review reported up to half of leu-
kemia and lymphoma patients may relapse.
There are long-term survivors. Doug Olson
in 2010 received the University of Pennsyl-
vania's CAR-T version for leukemia. The
researchers were frank - it had worked in
mice but they didn't know what would hap-
pen to him.
"Sitting here almost seven years later, I
can tell you it works," Olson, now 70, told
a recent meeting of the Leukemia and Lym-
Bannick, the Hutch patient treated in 2014,
recalls Maloney calling him "the miracle
man." He had some lingering side effects
that required blood-boosting infusions but
says CAR-T is "giving me a second life."
SCARY SIDE EFFECTS
"The more side effects you have, that sort
of tells everybody it's working," said Shefve-
land, who was hospitalized soon after his
treatment at Hutch when his blood pressure
collapsed. His last clear memory for days:
"I was having a conversation with a nurse
and all of a sudden it was gibberish."
As CAR-T cells swarm the cancer, an
immune overreaction called "cytokine release
syndrome" can trigger high fevers and plum-
meting blood pressure and in severe cases
organ damage. Some patients also experience
confusion, hallucinations or other neurolog-
Treatment is a balancing act to control
those symptoms without shutting down the
Experienced cancer centers have learned
to expect and watch for these problems.
"And, most importantly, we've learned how
to treat them," said Dr. Len Lichtenfeld of
the American Cancer Society, who is watch-
ing CAR-T's development.
FIGHTING SOLID TUMORS WILL BE HARDER
CAR-Ts cause collateral damage, killing
some healthy white blood cells, called B cells,
along with cancerous ones because both
harbor the same marker. Finding the right
target to kill solid tumors but not healthy
organ tissue will be even more complicated.
"You can live without some normal B cells.
You can't live without your lungs," Riddell
explained. Early studies against solid tumors
are beginning, targeting different antigens.
Time-lapse photos taken through a micro-
scope in Riddell's lab show those new CAR-T
cells crawling over aggressive breast cancer,
releasing toxic chemicals until tumor cells
shrivel and die.
CARs aren't the only approach. Research-
ers also are trying to target markers inside
tumor cells rather than on the surface, or
even gene mutations that don't form in
"It's ironic that the very mutations that
cause the cancer are very likely to be the
Achilles heel," NCI's Rosenberg said. And
studies are beginning to test CAR-Ts in com-
bination with older immunotherapy drugs,
in hopes of overcoming tumor defenses.
HOW WILL PATIENTS GET THE FIRST CAR-T
If the FDA approves Novartis' or Kite's
versions, eligible leukemia and lymphoma
patients would be treated at cancer centers
experienced with this tricky therapy. Their
T cells would be shipped to company fac-
tories, engineered, and shipped back. Grad-
ually, more hospitals could offer it.
Because only certain patients would qual-
ify for the first drugs, others would have to
search for CAR-T studies to try the treatment.
A drug industry report lists 21 CAR-T ther-
apies in development by a dozen companies.
"This is the hope of any cancer patient,
that if you stay in the game long enough,
the next treatment's going to be just around
the corner," said Shefveland, the Hutch
New frontier in cancer care:
In this photo taken March 29, 2017, Dr. David Maloney of the Fred Hutchinson Cancer
Research Center is greeted by patient Ken Shefveland, whose lymphoma was successfully
treated with CAR-T cell therapy. Immune therapy is the hottest trend in cancer care and its
next frontier is creating "living drugs" that grow inside the body into an army that seeks
and destroys tumors. (AP Photo)
Links Archive June 21st 2017 June 23rd 2017 Navigation Previous Page Next Page