Drs. Marko
Radic and Georg Schett Honored at FOCIS 2024 Meeting
SAN FRANCISCO, June 20, 2024 /PRNewswire/ -- The Lupus Research
Alliance (LRA) announced the recipients of the 2024 Lupus Insight
Prize to Marko Radic, Ph.D., The
University of Tennessee Health Science
Center, and Georg Schett, M.D., Friedrich-Alexander-Universität
Erlangen-Nürnberg, for their groundbreaking discoveries in
utilizing CAR T cell therapy to potentially revolutionize lupus
treatment. Drs. Radic and Schett were honored at a celebratory
award ceremony during the Federation of Clinical Immunology
Societies (FOCIS) 2024 meeting.
The Lupus Insight Prize is awarded to outstanding investigators
who have made a significant discovery in the last five years that
will advance our understanding of the development, diagnosis, or
treatment of lupus.
Revolutionizing Lupus Treatment Through CAR T
Cell Therapy
T cells are an essential pillar of the immune system— they mount
a response against harmful invaders, targeting and eliminating
pathogens like viruses and bacteria to protect us from infection.
Chimeric antigen receptor (CAR) T cell therapy involves
reprogramming a patient's own T cells to target and eliminate cells
contributing to the disease. CAR T cell therapy has garnered
significant attention and success in cancer treatment. Drs.
Marko Radic and Georg Schett have
made pioneering contributions to the field of CAR T cell therapies
for lupus, charting a new course in the treatment landscape and
offering hope for individuals with this complex condition.
"We are thrilled to award Drs. Marko
Radic and Georg Schett the 2024 Lupus Insight Prize for
their groundbreaking contributions to engineered cell therapies in
lupus," noted Teodora Staeva, Ph.D., Vice President and Chief
Scientific Officer at the LRA. "Their innovative application of CAR
T cell therapy offers unprecedented hope for a cure for individuals
living with lupus."
Pioneering CAR T Cell Therapy in Mouse Models of
Lupus
Dr. Marko Radic's seminal study,
partly funded by the LRA, highlighted the profound efficacy of CAR
T cells targeting CD19, a protein found on B cells. By using
CD19-targeted CAR T cells to deplete B cells, which serve as key
orchestrators of lupus disease, Dr. Radic's innovative approach
reduced disease progression in two mouse models of lupus. The CAR
T-treated mice lived longer, and several features of lupus were
eliminated or reduced substantially, including autoantibodies,
proteinuria (excess protein in the urine), and markers of
inflammation. Notably, the CAR T cells continued working several
months after administration. Dr. Radic's work laid the cornerstone
for exploring CAR T cell therapy as a promising avenue for treating
lupus in human patients, offering a glimpse into the potential of
immunotherapy for autoimmune diseases.
Dr. Radic will use his Lupus Insight Prize to study how a
process called trogocytosis affects the success or failure of CAR T
cell therapy. In some cases, when a CAR T cell attaches to its
target antigen (CD19 on the surface of B cells, in this case), the
CAR T cell can take in a piece of the target cell's membrane,
including CD19, without killing the target B cell. This process,
called trogocytosis (also known as "cell nibbling"), may lead to
exhaustion and death of the CAR T cells, potentially impacting the
effectiveness of CAR T therapy. Dr. Radic's proposed study will
guide the development of more effective cell therapies for people
with lupus.
Translating CAR T Cell Therapy to Clinical
Success
Building upon Dr. Radic's foundational research, Dr. Georg
Schett made significant strides in translating CAR T cell therapy
from preclinical studies to clinical application. In his
groundbreaking publication and follow-up study, Dr. Schett and
his team reported compelling outcomes from a single patient
followed by a small case series involving individuals with
refractory (resistant to treatment) lupus. Infusing CAR T cells
that target CD19 eliminated B cells from the blood by the second
day after CAR T administration. All individuals treated with
anti-CD19 CAR T cells showed a reduction in or disappearance of
lupus features including the presence of autoantibodies, nephritis
(kidney inflammation), and other manifestations such as arthritis,
fatigue, and lung issues.
In addition, four of the five patients reached a SLEDAI score (a
commonly used tool to measure disease activity) of 0, indicating no
detectable disease activity, and all five were able to stop taking
immunosuppressive drugs, achieving drug-free remission. Notably,
although their B cells returned about 100 days after CAR T cell
therapy, lupus remained absent, raising the possibility that the
immune system has been "rebooted" by the treatment, offering hope
for transformative treatments for people with lupus who are
resistant to conventional therapies.
CAR T cell administration effectively eliminated B cells from
the individuals' blood. However, if some self-reactive B cells
remain in the body's tissues, such as the lymph nodes, the immune
system may continue to malfunction. Dr. Schett has recently
developed a method to take tissue biopsies from people with lupus
to assess the extent of B cell depletion in their lymph nodes,
which are small lumps of tissue that are critical components of the
immune system. He will use his Lupus Insight Prize to analyze these
biopsies to assess how well the CD19-CAR T cell therapy was able to
eliminate B cells from this tissue. These findings could inform and
optimize treatment strategies, leading to improved long-term
disease management and better patient outcomes.
The groundbreaking use of CAR T cell therapy represents a
convergence of cutting-edge science and clinical innovation,
signaling a major shift in our approach to lupus management. As we
celebrate the remarkable achievements of both Drs. Radic and
Schett, we eagerly anticipate the continued advancements that will
emerge to unravel the complexities of lupus and improve outcomes
for people with lupus.
About Lupus
Lupus is a chronic, complex autoimmune disease that affects
millions of people worldwide. More than 90 percent of people with
lupus are women, often striking during the childbearing years of
15-45. Black, Hispanic, Indigenous, and Asian/Pacific Islander
people are disproportionately affected by lupus and are more likely
to experience severe lupus symptoms. Black, Hispanic, Indigenous,
and Asian/Pacific Islander people are disproportionately affected
by lupus and are more likely to experience severe lupus symptoms.
In lupus, the immune system, meant to defend against infections,
produces antibodies that mistakenly recognize the body's own cells
as foreign, prompting other immune cells to attack and potentially
damage organs such as the kidneys, brain, heart, lungs, blood,
skin, and joints.
About the Lupus Research Alliance
The Lupus Research Alliance is the largest non-governmental,
non-profit funder of lupus research worldwide. The organization
aims to transform treatment by funding the most innovative lupus
research, fostering diverse scientific talent, and driving
discovery toward better diagnostics, improved treatments, and
ultimately, a cure for lupus. Because the Lupus Research Alliance's
Board of Directors funds all administrative and fundraising costs,
100% of all donations goes to support lupus research
programs. For more information, please visit the LRA at
LupusResearch.org and on social media at: X, Facebook,
LinkedIn, and Instagram.
CONTACT:
Margy Meislin
mmeislin@lupusresearch.org
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SOURCE Lupus Research Alliance