The Lupus Research Alliance (LRA) has awarded inaugural grants totaling approximately $4.5 million to 11 researchers focused on developing next-generation engineered cell therapies for lupus. The new Targeted Research Program on Engineered Cell Therapies for Lupus (TRP-ECT) aims to support the development of safe, accessible cellular treatments that could potentially reset the immune system in lupus patients.
The initiative follows promising clinical results showing complete remission in lupus patients treated with CD19-targeted chimeric antigen receptor (CAR) T cell therapy who had not responded to previous treatments. These engineered cell therapies involve modifying a patient's own T cells to recognize and attack disease-causing cells.
"The establishment of the TRP-ECT marks a significant milestone in our mission to advance innovative treatments for lupus," noted LRA Chief Scientific Officer Teodora Staeva, PhD. "By supporting cutting-edge research in engineered cell therapies, we are paving the way for breakthroughs that could significantly improve the lives of those affected by this challenging disease."
Preclinical Research Projects
Eight researchers received grants of up to $300,000 over two years to conduct preclinical studies:
Dr. Reuben Benjamin of King's College London is developing a streamlined CAR T cell therapy that can be produced in just three days, potentially addressing current barriers of high cost and lengthy manufacturing times. This could make treatment more widely accessible to lupus patients.
Dr. Vijay Bhoj from the University of Pennsylvania's Perelman School of Medicine is working on a more selective approach that targets only age-associated B cells (ABCs), which are linked to lupus pathology. This precision targeting could induce lasting remission with fewer side effects than current CAR T therapies that eliminate all B cells, including protective ones.
Dr. Leslie Kean of Boston Children's Hospital has engineered regulatory T cells (Tregs) with CARs that recognize OX40L, a molecule found on immune cells in active lupus. These "OX40L-CAR-Tregs" will be tested in human cells and mouse models, potentially offering a new therapeutic approach.
Dr. Richard O'Neil at the Medical University of South Carolina is investigating CAR T cell therapy without lymphodepletion—the chemotherapy pretreatment that can cause severe side effects. His novel method could simplify patient management and reduce treatment complications.
Dr. Joshua Ooi from Monash University is scaling up the manufacturing process for Sm-Tregs, engineered regulatory T cells that target a key lupus protein. His previous work showed these cells could dampen inflammation and halt kidney injury in lupus models.
Dr. Reshmi Parameswaran of Case Western Reserve University is engineering natural killer (NK) cells to target three molecules on autoreactive B cells. These "BAFF-CAR NK" cells, derived from healthy donors, could provide an "off-the-shelf" therapy that's potentially less expensive and safer than current options.
Dr. Stanley Riddell at Fred Hutchinson Cancer Center has designed new chimeric T cell receptors (ChTCRs) that don't trigger cytokine production, potentially reducing toxicity associated with CAR T therapy. His animal model studies aim to improve safety and efficacy for lupus patients.
Dr. Mark Shlomchik from the University of Pittsburgh is testing CAR T cell therapy that selectively eliminates pathogenic age-associated B cells while sparing protective B cells, potentially offering a more precise treatment approach.
Clinical Trial Ancillary Studies
Three researchers received grants of up to $600,000 over two years to conduct studies alongside ongoing or completed clinical trials:
Dr. Ricardo Grieshaber-Bouyer at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) will analyze blood and tissue samples from over 15 refractory lupus patients who achieved drug-free remission after CD19 CAR T cell therapy. His comprehensive study aims to understand how the therapy resets the immune system.
Dr. Shaun Jackson of Seattle Children's Hospital is analyzing samples from the REACT-01 clinical trial, the first U.S. trial evaluating CAR T cell therapy in children with lupus. His work could inform treatment strategies for pediatric and young adult patients.
Dr. Ignacio Sanz at Emory University is conducting detailed analyses of B cell depletion and recovery in CAR T-treated patients to understand what determines successful response, potentially helping identify patients most likely to benefit from future treatments.
Addressing a Critical Unmet Need
Lupus affects millions worldwide, with 90% of patients being women, most often diagnosed between ages 15-45. The autoimmune disease disproportionately affects Black, Latinx, Indigenous, Asian and Pacific Islander populations, who typically experience more severe symptoms.
Current treatments often involve long-term immunosuppression with significant side effects. The engineered cell therapies being developed through this initiative aim to reset the immune system, potentially offering drug-free remission and improved quality of life for lupus patients.
"These innovative approaches could transform lupus treatment by addressing the root causes of immune dysregulation rather than just managing symptoms," said Dr. Staeva. "The diversity of approaches being funded reflects our commitment to exploring multiple pathways toward better outcomes for patients."
Future Implications
The research funded through the TRP-ECT program could have far-reaching implications beyond lupus. Advances in engineered cell therapies for lupus may inform treatments for other autoimmune conditions with similar immune system dysregulation.
As these projects progress, they may help overcome current limitations of cell therapies, including manufacturing complexity, cost, and accessibility. The development of "off-the-shelf" options and faster production methods could make these potentially transformative treatments available to more patients.
The Lupus Research Alliance, as the largest non-governmental, non-profit funder of lupus research worldwide, continues its mission to transform treatment through innovative research. With 100% of donations going directly to research programs, the organization remains committed to improving diagnostics, treatments, and ultimately finding a cure for lupus.
