O'Neal Comprehensive Cancer Center Magazine Spring 2019 | 页面 9

The whole process, from the collection of the patient’s
T cells to the infusion of the patient’s modified cells can
range between three and six weeks, which is why Mehta
says it’s important for doctors to find qualified patients
who are stable enough to wait for the procedure and
undergo the necessary chemotherapy.
James Lacey, of Mobile — the first patient to undergo
CAR T-cell therapy in Alabama — was treated successfully
with CAR T therapy. Originally diagnosed with follicular
non-Hodgkin lymphoma in 2007, Lacey’s lymphoma had
transformed to diffused large B cell lymphoma, and after
years of chemotherapy, bouts of remission and several
experimental therapies, the cancer was no longer
responding to treatments. Lacey opted to be treated
with CAR T cells by his doctor, Andres Forero, M.D.
CAR T-CELL THERAPY
UAB offers CAR T-cell therapy, a new treatment that adapts a
patient’s own immune system to fight cancer
By Kendra Carter
Our bodies are full of fighters. In a healthy immune
system, the body is full of immune cells which are
responsible for its first line of defense for killing
infections.
“For years scientists knew that the immune system
also keeps cancer in check,” says Amitkumar Mehta,
M.D., associate scientist in the O’Neal Comprehensive
Cancer Center at UAB and assistant professor in the
UAB Division of Hematology and Oncology. “But that
concept has evolved and expanded in the last ten years,
giving researchers the idea that we could manipulate the
immune system to keep the cancer under control.”
So what if those immune cells could be trained to fight
certain types of cancer? Advances in immunotherapy—
using the body’s own immune system, especially
T cells—is now tested for treatment of B-cell lymphoma
and multiple myeloma in clinical trials at the O’Neal
Comprehensive Cancer Center. Scientists have now
developed techniques to modify the T Cells so they can
recognize cancer cells in a targeted way, called chimeric
antigen receptor, better known as CAR T-cell therapy.
“THE ESSENTIAL PILLAR”
Immunotherapies, like CAR T-cell therapy, are becoming
the essential pillar of cancer care, joining the ranks of
surgery, chemotherapy, radiation and other targeted
treatments.
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O ’ N E A L CO M PR EH EN S I V E C A N C ER C EN T ER AT UA B
In the CAR T approach, a patient’s T cells are collected
from their blood through a process called apheresis.
Those cells are then sent to a laboratory where they’re
genetically modified so they can express the chimeric
antigen receptor protein through a viral transfection,
which will target only the cancer cell.
Once the cancer cells are modified, the patient
undergoing the CAR T therapy receives three days of
chemotherapy treatment to prepare their bodies to
accept the modified T cells.
“The chemo treatment is not targeted toward treating
the cancer, but to deplete the patient’s remaining T cells
so their body is hungry enough to accept the modified
T cells,” says Mehta, associate director for the CAR T
program at UAB.
When the modified T cells are then put back into the
patient’s bloodstream, they grow in number and attach
to the target in the cancer cell for which they were
developed. In the case of the B cell lymphomas, the
CD19 is the target. In the case of multiple myeloma,
B-cell maturation antigen (BCMA) is the target. Both
targets are located on the surface of cancer cells. The
binding activates the T cells and induces cancer cell
death, Mehta says. Patients are monitored for several
days post-therapy to watch for toxicities, and for three
months post treatment to monitor their response to
therapy.
Lacey says physicians noticed results from the therapy
almost immediately, and he’s been in remission post
CAR T treatment for more than two years.
“Dr. Forero noticed the day after I received the infusion
that the lymph nodes in my neck had receded a little
bit,” Lacey says. “It was the magic bullet that started to
fire right away.”
For Wayne Edwards, being able to tend to his flower
garden and taking long walks around the lake with his
grandson Barrett, has been an important development
in his life post-treatment.
Edwards, a retired deputy sheriff in Montgomery
County, underwent the CAR T therapy last year. He
had been diagnosed with stage four non-Hodgkin
lymphoma in 2013 in Montgomery, and, after a round of
chemotherapy and a brief remission, Edwards’ disease
recurred and spread. He says treatment was ineffective
at that point, so he was referred to Mehta at UAB.
After progression with another research agent, before
Mehta approached him about CAR T-cell therapy.
“Dr. Mehta sat down with me and my wife Sandi to
explain the all the possible risks and benefits of the CAR
T treatment with us, and I felt at that point that, really,
I had nothing to lose. I figured that if it didn’t help me,
maybe they would be able learn something that could
help another patient.
“When he told me about the T cell therapy, I was excited.
It’s hard to explain, but it was an amazing opportunity
when I didn’t have hope,” Edwards says.
A QUALITY APPROACH
While CAR T is a newer method of immunotherapy, UAB
has been using other cellular therapies, such as bone
marrow transplants for more than 20 years. The two
therapies are linked because they serve similar patient
populations and require similar infrastructure, including
apheresis, cell processing laboratory and dedicated
inpatient and outpatient facilities, says Luciano J. Costa,
M.D. a scientist in the O’Neal Comprehensive Cancer
Center and director of the newly established Immune
Effector Cell Therapy program.
For that reason, the leadership of UAB’s Division of
Hematology and Oncology created this Immune Effector
Therapy group, combining the burgeoning CAR T-cell
program with the existing UAB Bone Marrow Transplant
and Cellular Therapies program.
Costa says that in doing so, leaders are able to develop
policies, procedures and training that involves all
physicians, support staff, nurses, nurse coordinators
and advance practice providers to provide CAR T-cell
therapy to patients.
“Dr. Forero
noticed the day
after I received
the infusion that
the lymph nodes
in my neck had
receded a little
bit. It was the magic bullet that
started to fire right away.”
— James Lacey
UAB has a longstanding commitment to quality in this
arena, Costa says, citing the hospital’s accreditation
status with the Foundation for the Accreditation of
Cellular Therapy (FACT) for the past 15 years.
“This attests to our patients that UAB follows the highest
standard of quality and that our processes are optimized
to maximize patient safety and improve outcomes,”
Costa says.
The expansion of this cellular therapy team and the
commitment to accreditation standards will help UAB
in offering CAR T-cell therapy to patients with other
cancers, Costa says. The Bone Marrow Transplant-
Immune Effector Cell Therapies Program is also in
process for certification for treating patients with
commercial products (CAR T-cell treatments that have
successfully completed clinical trials and received FDA
approval). Mehta says this commercial certification
would mean patients with certain B cell aggressive
lymphomas would be able to be treated with CAR
T-cell therapy as standard of care like all other cancer
treatments—a move that could be finalized in the coming
months.
UAB.EDU/CANCER
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