Lupus Research Alliance, Genentech fund immune-resetting studies
Grants support researchers translating early CAR T-cell therapy success into care
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The Lupus Research Alliance and Genentech have launched a new funding program to support three research projects focused on developing immune-resetting CAR T-cell therapies for lupus. The initiative seeks to deepen the scientific understanding of how these treatments work to help achieve longer-lasting disease remission.
CAR T-cell therapy is currently being studied in severe lupus after early trials showed that some patients with difficult-to-treat forms of the disease achieved rapid, lasting remission and were able to stop other medications. The newly funded studies will address critical questions about how the therapy resets the immune system and why remission lasts in some patients but not in others.
The projects are the first to receive support through the Lupus Research Alliance-Genentech Award on Immune Resetting Therapies for Lupus (LGA-IRT). Each award provides $150,000 per year for up to two years to advance therapies that may eventually be both effective and accessible for people living with lupus.
Understanding the role of B-cells in lupus
“Moving from early breakthrough clinical trials to effective therapies requires a strong scientific foundation,” Teodora Staeva, PhD, chief scientific officer of the Lupus Research Alliance, said in a press release. “By supporting these studies with our long-standing partner Genentech, we are deepening our understanding of immune reset to ultimately make these therapies safer and more durable for people affected by this devastating disease.”
Lupus is a chronic autoimmune disease in which the immune system mistakenly attacks the body’s own tissues. These attacks can affect many parts of the body, including the kidneys, brain, heart, lungs, skin, blood, and joints. B-cells, a type of immune cell, play a central role in lupus because they produce autoantibodies, which are self-reactive antibodies that drive inflammation and tissue damage.
CAR T-cell therapy is a type of immune therapy originally developed for cancer that has since been extended to treat autoimmune diseases. The process involves collecting a person’s own immune T-cells and modifying them in a laboratory to produce a chimeric antigen receptor (CAR) that targets a specific protein once the cells are infused back into the patient. In ongoing trials for severe lupus, the modified CAR T-cells specifically target a protein called CD19 on the surface of harmful B-cells.
One of the awarded projects is led by Anne Davidson of The Feinstein Institutes for Medical Research. The project will use mouse models of lupus to study why CAR T-cell therapy can lead to long-lasting remission in some cases but cause a relapse in others.
Her team will examine whether some plasma cells, which are antibody-producing cells that do not carry the CD19 target, manage to survive the treatment. Additionally, they will assess whether inflammation persists or recurs after therapy. The goal is to identify immune conditions associated with sustained remission or disease recurrence to inform future treatment strategies.
Panagiotis Garantziotis, MD, PhD, of Uniklinikum Erlangen in Germany, will lead a second project studying blood and bone marrow samples from lupus patients treated with CAR T-cells. His team will compare them over the course of one year with samples from patients receiving standard B-cell-targeting therapies. The goal is to clarify how CAR T-cell therapy resets the immune system, which scientists hope may help guide the development of better treatments for difficult-to-treat lupus.
Finally, the third project, led by Eric Meffre, PhD, at Stanford University, will investigate whether CAR T-cell therapy successfully helps restore immune tolerance, the process that normally prevents the immune system from attacking the body. In lupus, this safeguard fails. Meffre’s project will test whether CAR T-cell therapy fixes this problem at its source or instead strengthens mechanisms that keep potentially harmful B-cells under control.
