Engineered Immune Cells Produce Complete Response in Child with an
Aggressive Pediatric Leukemia
ATLANTA, Dec. 9, 2012 /PRNewswire/ -- By reprogramming a
7-year-old girl's own immune cells to attack an aggressive form of
childhood leukemia, a pediatric oncologist has achieved a complete
response in his patient, who faced grim prospects when she relapsed
after conventional treatment. The innovative experimental therapy
used bioengineered T cells, custom-designed to multiply rapidly in
the patient, and then destroy leukemia cells. After the treatment,
the child's doctors found that she had no evidence of cancer.
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Pediatric oncologist Stephan A. Grupp, M.D., Ph.D., of The
Children's Hospital of Philadelphia, and colleagues from the
University of Pennsylvania presented updated results of the
clinical trial involving these engineered cells at the American
Society of Hematology (ASH) annual meeting today in Atlanta. Grupp is the director of
Translational Research for the Center for Childhood Cancer Research
at The Children's Hospital of Philadelphia, and a professor of Pediatrics at
the Perelman School of Medicine at the University of Pennsylvania.
Grupp's research builds on his ongoing collaboration with
Penn scientists who originally
developed the modified T cells as a treatment for B-cell leukemias.
The Penn team reported on early results
of a trial using this cell therapy in adult chronic lymphocytic
leukemia (CLL) patients in August of 2011. Carl H. June, M.D., of
the Perelman School of Medicine at the University of Pennsylvania, leads this research
group, which is presenting new data at the ASH meeting showing that
nine of 12 patients with advanced leukemias in the clinical trial,
including two children, responded to treatment with CTL019
cells.
One of the nine responding patients is the 7-year-old with acute
lymphoblastic leukemia (ALL). Grupp and Penn colleagues adapted the treatment to combat
ALL, the most common childhood leukemia, and also the most common
childhood cancer. Although physicians can cure roughly 85 percent
of ALL cases, the remaining 15 percent of such cases stubbornly
resist treatment.
The CTL019 therapy, formerly called CART19, represents a new
approach in cancer treatment. T cells are the workhorses of the
immune system, recognizing and attacking invading disease cells.
However, cancer cells fly under the radar of immune surveillance,
evading detection by T cells. CAR T cells (chimeric antigen
receptor T cells) are engineered to specifically target B cells,
which become cancerous in certain leukemias, such as ALL and CLL,
as well as types of lymphoma, another cancer of the immune
cells.
CD19 is a protein found only on the surface of B cells. By
creating an antibody that recognizes CD19, and physically
connecting that antibody to T cells, the researchers have created a
guided missile that locks in on and kills B cells, thereby
attacking B-cell leukemia.
In using the CTL019 treatment in his pediatric patient, Grupp
found that the very activity that destroyed leukemia cells also
stimulated a highly activated immune response called a cytokine
release syndrome. The child became very ill and had to be admitted
to the intensive care unit.
Grupp and his team decided to counteract these toxic side
effects by using 2 immunomodulating drugs that blunted the
overactive immune response and rapidly relieved the child's
treatment-related symptoms. These results were effective enough
that this approach is now being successfully incorporated into
CTL019 treatments for adults as well.
The immunomodulating drugs did not interfere with the CTL019
therapy's anti-leukemia benefits, which have persisted 6 months
after the infusion of cell therapy. This persistence is essential,
because the engineered T cells remain in the patient's body to
protect against a recurrence of the cancer.
"These engineered T cells have proven to be active in B cell
leukemia in adults," said Grupp. "We are excited to see that the
CTL019 approach may be effective in untreatable cases of pediatric
ALL as well. Our hope is that these results will lead to widely
available treatments for high-risk B cell leukemia and lymphoma,
and perhaps other cancers in the future."
"This type of pioneering research addresses the importance of
timing when considering experimental therapies for relapsed
patients," added Susan R. Rheingold,
M.D., one of the leaders in the Children's Hospital program for
children with relapsed leukemia. "To ensure newly relapsed
patients with refractory leukemia meet criteria for options like
CTL019, we must begin exploring these innovative approaches earlier
than ever before. Having the conversation with families
earlier provides them more treatment options to offer the best
possible outcome."
In August 2012, Novartis acquired
exclusive rights from Penn to CART-19,
the therapy that was the subject of this clinical trial and which
is now known as CTL019.
For more information about the engineered T cell clinical
trial at the University of
Pennsylvania, or interviews with Penn Medicine lead
researcher Carl June, M.D., or
investigators David Porter, M.D., or
Michael Kalos, Ph.D., contact
Holly Auer, cell: 215-200-2313, or
holly.auer@uphs.upenn.edu.
"CD19-Redirected Chimeric Antigen Receptor T (CART19) Cells
Induce a Cytokine Release Syndrome (CRS) and Induction of Treatable
Macrophage Activation Syndrome (MAS) That Can Be Managed by the
IL-6 Antagonist Tocilizumab (toc)"
--Abstract #2604
presented, Sun., Dec. 9, 2012,
6 p.m. ET; Hall B1-B2, Level 1,
Building B--
About the Cancer Center at The Children's Hospital of
Philadelphia: The Children's
Hospital of Philadelphia cares for
more children with cancer than any other general pediatric hospital
in the United States. Its large
basic and clinical research programs are particularly strong in
pediatric neuro-oncology, neuroblastoma, leukemia and lymphoma, and
sarcomas. Of all pediatric institutions, Children's Hospital
enrolls the most patients in national clinical trials, working in
close collaboration with national organizations such as the
Children's Oncology Group. Physicians at Children's Hospital have
had pioneering roles in developing international standards for
diagnosing and treating neuroblastoma, and in developing programs
for survivors of childhood cancer.
Contact: Rachel
Salis-Silverman
The Children's Hospital of Philadelphia
Cell: (267) 970-3685
Salis@email.chop.edu
SOURCE The Children's Hospital of Philadelphia