After a decade researching causes and treatments for lupus, Dr. Marko Radic, left, received the 2024 Lupus Insight Prize recognizing and honoring significant scientific insights relevant to understanding the disease. "I feel a very strong ethical commitment to do something worthwhile with my work," he said.

Ten years ago, Marko Radic, PhD, laced up his walking shoes to participate in the Virginia Davis Memorial Walk/Run for Lupus, a fundraiser to support the Lupus Foundation of America. An associate professor in the UT Health Science Center's Department of Microbiology, Immunology and Biochemistry, Dr. Radic had spent his research career up to that point focusing on basic immunology and the mechanisms that lead to autoimmune diseases. He never suspected that morning in Overton Park would spur a major shift in his research approach.

But walking alongside and interacting with lupus patients and their families, Dr. Radic was struck by how severely the disease affected their daily lives. "The most common form of lupus, systemic lupus erythematosis, can affect nearly all your organ systems: cardiovascular, respiratory, GI, your joints, your skin, your musculature," he said. He was also disheartened when explaining his work to them. "No matter how much a scientist tries to consider lay language and explain things from first principles, and no matter if a patient perfectly understands all the basic biology questions, they still approach things from their own point of view. Their main concern is they have an incurable illness and a reduced life expectancy. I realized some of our basic research wasn't translating to them or really impacting their daily struggles."

His experience at the event motivated him to switch his approach to impact patient health and well-being directly.

"At the time, I was following an observation that was done by researchers in Pennsylvania. Dr. Carl June at the University of Pennsylvania had introduced a cell therapy that was very good at eliminating cancerous B cells (a type of immune cells thought to be responsible for lupus manifestations). In many autoimmune diseases you can find antibodies in the plasma that react with your own tissues. So eliminating B cells seemed like a good way to test the role of B cells in lupus. We proposed to do that in two different mouse models of lupus, and set out the experiments with funding from the Lupus Research Alliance (LRA) in New York City."

The study was a collaboration between various faculty in his department, students in Dr. Radic's lab, and the College of Pharmacy. "To all of our amazement, the study worked out quite well. We were able to show that CAR-T cells, the name of this technology, was able to remove B cells and really eliminate all the classical clinical signs of lupus in patients."

Dr. Radic authored a paper on the landmark study demonstrating applicability of CAR-Ts in autoimmune diseases, which was published in Science Translational Medicine in 2019. He is now recognized as a thought leader in autoimmune CAR-T cell therapy, antibody-mediated disorders and designing CAR-T studies.

"I think patients' perspectives, involvement, and questions shape many research efforts in the field."

Dr. Marko Radic

"What's really amazing and gratifying is to see that within a few short years this same approach was tried in clinical trials run first in Germany, and now increasingly in China. Recently, two companies in the U.S. were FDA cleared to start CAR-T cell therapies in lupus patients. Obviously, as clinical trials, only a handful of patients will be treated, but so far the results from the group in Germany are quite stunning, showing you can eliminate B cells but also alleviate all of the presentations of lupus in the treated patients. So we're quite excited."

The Lupus Research Alliance, which helped fund Dr. Radic's seminal study, is again supporting his work. The alliance selected him to receive the 2024 Lupus Insight Prize recognizing and honoring significant scientific insights relevant to understanding the causes, pathogenesis, or treatment of lupus. The prize aims to stimulate further advances leading to improved outcomes for lupus patients and ultimately to a cure.

Dr. Radic was honored at a public ceremony at the FOCIS (Federation of Clinical Immunology Societies) Annual Meeting in San Francisco on June 19, 2024. He plans to use his award 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.

Dr. Radic's gratitude for this award and support is compounded by his compassion and concern for how deeply lupus affects his adopted city. "Other diseases, may be less prevalent or less impactful, receive more funding," he says. "But there are a number of contributing factors which make our particular metro area an epicenter of this condition. Lupus preferentially targets ethnic minorities, mostly females. Because females in general may not be receiving the necessary medical care, and because of the difficulty of diagnosing the disease, it's a particular burden in people living here.

"Another point worth mentioning regarding local conditions is that lupus as a disease is heterogeneous among different patients," he continues. "Different patients may present with different manifestations. So on average, it takes over a year to two years to get your initial diagnosis. It's even longer for underprivileged individuals in our in our city. Some patients only get diagnosed very late in the disease."

Emphasizing the role of the patient voice in research remains central to Dr. Radic as he continues his cutting-edge work to further develop effective immunotherapy. "I think patients' perspectives, involvement, and questions shape many research efforts in the field," he said. "I feel a very strong ethical commitment to do something worthwhile with my work."

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