Novel cell therapy treatments offer promise to immune-compromised children
April 18 2024 - 10:30AM
In a first-of-its-kind clinical trial, researchers found that
intravenous therapies made from virus-specific T-cells (VST) can
effectively treat immunocompromised pediatric patients, far
surpassing the current standard of care, according to new research
published in Nature Communications. More
than 60% of patients in the phase 2 clinical trial led by
investigators from Children’s National Hospital and Huntsman Cancer
Institute responded to the innovative VST therapy. This new
treatment uses blood from healthy donors to manufacture a highly
specialized immune therapy that, when given to immune-compromised
patients, prompts their immune system to fight off potentially
life-threatening viruses, including cytomegalovirus, Epstein-Barr
and adenovirus. Without this therapy, estimates suggest that less
than 30% of patients would recover, using standard
protocols.
“A vast majority of our
patients not only responded to the therapy, but they were able to
come off their antivirals, which come with extensive side effects,”
said Michael Keller, M.D., the paper’s first author and the
Translational Research Laboratory director at the Children’s
National Cell Enhancement and Technologies for Immunotherapy (CETI)
program. “This promising data suggests hope for patients with rare
immune-compromising diseases that leave them vulnerable to so much
in the world.”
The study brings together
experts from the Pediatric Transplantation and Cell Therapy
Consortium (PTCTC) and the Primary Immune Deficiency Treatment
Consortium (PIDTC) to create the first multi-center,
pediatric-consortium trial of adoptive T-cell therapies for
viruses. It also represents one of the first to include critically
ill patients, who are often excluded from research.
Working alongside
Catherine Bollard, M.D., M.B.Ch.B., director of the Center for
Cancer and Immunology Research (CCIR), Dr. Keller and the CCIR team
helped build an internationally recognized program, pioneering
therapies to prevent complications from viral infections in
immunocompromised patients. This includes patients with congenital
immune deficiency and others who have undergone bone marrow
transplantation for malignancies or non-malignant conditions, such
as sickle cell disease.
While doctors can treat
some immune-compromised patients for infections with standard
antivirals, a small fraction don’t respond. Children’s National is
one of a handful of hospitals in the country that has options. Over
the last several decades, researchers have found ways to develop
VST therapies made from banked T-cells, a more advanced application
of how donated red blood cells are used to treat
anemia.
In 2017, Drs. Keller and
Bollard started collaborating with Michael Pulsipher, M.D.—now with
Intermountain Primary Children’s Hospital and the Huntsman Cancer
Institute at the University of Utah—to create a multi-institute
clinical study. They combined the expertise at Children’s National
in producing and banking cell therapy products with the community
built around the PTCTC. Ultimately, they launched a clinical trial
that was open to 35 centers in the U.S., enrolling 51 patients at
22 hospitals from 2018-2022.
“We wanted to prove that
this potentially life-saving therapy could be given safely at
regional pediatric centers that had never been able to use this
approach before,” said Dr. Pulsipher, who served as the study’s
co-principal investigator with Dr. Keller. “We united top experts
in this area from the PTCTC and PIDTC and successfully treated some
of the most challenging patients ever treated with this approach.
Our findings helped define who can benefit the most from this
therapy, paving the way for commercial development.”
The Good Manufacturing
Practices (GMP) laboratory at Children’s National, led by Patrick
Hanley, Ph.D., provided suitable VST therapies for 75 of 77
patients who requested to join the study. Clinical responses were
achieved in 62% of patients who underwent stem cell transplants and
in 73% of patients who were treated with VST and evaluated one
month after their infusion. The paper laid out risks and clinical
factors impacting outcomes when third-party donors are used to
manufacture the VST therapies.
Given that researchers
are only beginning to develop cell therapies, work remains to
understand the many ways they interact with the immune system. In a
separate paper also recently published in Nature Communications,
members of the multi-institute team documented a case of an infant
with severe combined immune deficiency, who faced extremely rare
side effects when the VST treatment interfered with her donor bone
marrow graft. The case led the team to work with the Food and Drug
Administration to identify criteria for VST donors enrolled in this
study to mitigate complications.
In the decade ahead, Dr.
Bollard sees promise in cell therapies for patients with cancer,
immune deficiencies after transplant and dozens of other disorders,
including genetic and autoimmune diseases. “Future studies will
continue to look at ways to optimize the manufacturing, the
administration and the long-term outcomes for these therapies—and
to enhance the lifelong impact on our patients,” she said. “When we
pair human ingenuity with the power of technology, I see tremendous
potential.”
Note: This study was
funded with a nearly $5 million grant from the California Institute
of Regenerative Medicine and was run through the operations center
at the Children’s Hospital of Los Angeles, where Dr. Pulsipher was
formerly on faculty.
Media contact:
Katie Shrader | media@childrensnational.org
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Katie Shrader
Children's National Hospital
media@childrensnational.org