Killer T-cell therapy shows promise against leukemia

A cancer-killing therapy that engineers a
patient’s own immune cells to wipe out chronic
lymphocytic leukemia (CLL)
A cancer-killing therapy that engineers a
patient’s own immune cells to wipe out chronic
lymphocytic leukemia (CLL) has shown long-term
success in a handful of people, a US study said
Wednesday.
Experts said the approach is on the cutting edge
of a growing field known as immunotherapy,
which coaxes the body to kill off cancer and may
someday revolutionize oncology by ending the
use of toxic chemotherapy.
The method, known as CTL019, was developed
by the University of Pennsylvania’s Abramson
Cancer Center and Perelman School of Medicine,
which is now reporting the first long-term results
on a group of 14 initial patients.
Eight of the adults enrolled in the study (57
percent) responded to the treatment, with four
going into long-term remission and the other four
experiencing a partial response, said the findings
in the journal Science Translational Medicine.
The first person to be treated recently marked
five years cancer-free. Two others have made it
to four and half years with no sign of cancer’s
return. The fourth was in remission for 21
months, then died of an infection following a
surgery that was unrelated to the leukemia.
“Our tests of patients who experienced complete
remissions showed that the modified cells
remain in patients’ bodies for years after their
infusions, with no sign of cancerous or normal B
cells,” said senior author Carl June, professor of
immunotherapy in Penn’s department of
pathology and laboratory medicine.
“This suggests that at least some of the CTL019
cells retain their ability to hunt for cancerous
cells for long periods of time.”
Four of the patients (29 percent) responded to
the therapy, for a median of seven months, but
their cancer eventually returned.
– How it works –
Researchers first reported initial results on three
adult patients in 2011, showing that two of the
three had gone into remission in the first year of
treatment.
Normally, the immune system tries to attack
cancer but fails because cancer can evade the
body’s defenses.
The experimental therapy is made from patients’
own immune cells, sometimes known as T-cells,
which are collected by researchers and
reprogrammed to better search for and kill
cancer.
They are modified to contain a protein known as
a chimeric antigen receptor (CAR), which targets
the CD19 protein found on the surface of
cancerous B cells.
After the immune cells are collected and re-
engineered, the patient undergoes chemotherapy
to wipe out their current immune system before
they are re-infused with their newly empowered
immune cells.
Jacqueline Barrientos, a medical oncologist at
the North Shore-LIJ Cancer Institute who was
not involved in the study, described the approach
as “revolutionary,” because of its ability to wipe
out CLL for years.
“This is an exciting time,” she told AFP, adding
that many experts think June is likely to win the
Nobel Prize someday for shepherding in a new
era of cancer treatment.
– ‘Pioneers’ –
Other experts say the success of immunotherapy
— particularly CAR treatments for leukemia and
lymphoma — raises new questions about what it
could mean to be “cured” of cancer.
“There is certainly a potential for a cure here in
some of these patients who have had prolonged
remissions,” said Joshua Brody, director of the
lymphoma immunotherapy program at Mount
Sinai Hospital.
“What if they are not cured but they have this
ongoing therapy that stays inside of them and
keeps fighting back cancer every time cancer
rears its head?” added Brody, who was not
involved in the study.
“This would be close to a cure from the patient’s
perspective.”
Of course, the treatment did not work for
everyone. In addition to the four patients whose
cancer returned, six others in the 14-person trial
did not respond at all.
Scientists are working hard to figure out why
that group’s modified T-cells did not expand in
their bodies at the same rate as in those who
went into long-term remission.
“The patients in this study are pioneers, whose
participation has given us a foundation of
knowledge and experience on which to build this
new approach to help more patients,” said lead
author David Porter, director of Blood and
Marrow Transplantation in Penn’s Abramson
Cancer Center.

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