A Guide to Conducting Car T-Cell Trials for Patients With SLE

– Experts say CAR T-cells hold major promise, especially for patients with lupus

T-cells can be very helpful in the treatment of autoimmune disease as well as different types of cancer. T-cells can push out the B cells which make autoantibodies in lupus. Removing the B cells which make the antibodies and create the autoimmune environment is a worthy goal, but obviously this new therapy can be challenging and more needs to be done to see the safety and efficacy in lupus. – Dr. Robert Katz, LSI’s Board Chair and Medical Advisory Board Chair.

Leading rheumatologist-researchers have assembled a comprehensive guide for initiating and managing CAR T-cell trials for systemic lupus erythematosus (SLE). It appears in ACR Open Rheumatology.

Experts recommend a multi-tiered approach involving assessing current capabilities, ensuing regulatory compliance and resource management, among other steps.

Saira Sheikh, MD, is a lupus researcher and the Linda Coley Sewell Distinguished Professor of Medicine at the University of North Carolina at Chapel Hill. Roberto Caricchio, MD, is the Myles J. McDonough Chair in Rheumatology and Chief of the Division of Rheumatology at UMass Chan Medical School. Both served as co-authors of the report and recently answered questions from the Reading Room. The exchange was edited for length and clarity.

For those who have not yet reviewed the report, what was the motivation behind it and what was its main objective?

Caricchio and Sheikh: Chimeric antigen receptor (CAR) T-cell therapy, initially developed as a groundbreaking cancer treatment for refractory blood malignancies, is now emerging as a promising therapeutic strategy beyond oncology. Originally designed to reprogram a patient’s own T-cells to recognize and eliminate malignant cells, this powerful approach is being successfully repurposed to treat severe autoimmune diseases refractory to conventional therapies.

Early clinical experiences in conditions such as SLE demonstrate that CAR T-cells can selectively eliminate pathogenic immune cells, leading to deep and often durable disease remission. This evolution underscores a paradigm shift — from targeting cancer alone to redefining immune modulation — highlighting CAR T-cell therapy’s transformative potential across diverse immune-mediated diseases.

While CAR T-cell therapy has been revolutionary in the field of oncology, its application to autoimmune diseases requires fundamental adaptation. Autoimmune indications differ from cancer in therapeutic goals, target biology, risk tolerance, and long-term management, necessitating disease-specific approaches to conditioning, toxicity mitigation, patient selection, and durable immune reprogramming rather than cytotoxic eradication. Most centers are currently not prepared to deliver CAR T-cell therapy for autoimmune diseases. Existing infrastructure, clinical workflows, and regulatory frameworks are largely oncology-centric and do not reflect the needs of autoimmune patient populations. Successful implementation will require dedicated training of multidisciplinary teams and the development of new institutional pathways.

Our recently published paper addresses this gap by outlining a practical roadmap for adapting CAR T-cell therapy from oncology to autoimmunity, including center readiness, workforce training, trial design, safety monitoring, and long-term follow-up, with the goal of enabling safe, scalable, and equitable clinical adoption.

How would you describe or summarize the guide you developed?

Caricchio and Sheikh: At its core, this is an implementation guide designed to serve as a practical roadmap for clinicians, investigators, and institutions considering CAR T-cell therapy trials in autoimmune disease. It walks through the full continuum of care — from assessing institutional readiness and assembling a multidisciplinary team, to patient selection, inpatient and outpatient management, toxicity monitoring, and long-term follow-up. The guide emphasizes translating established cell-therapy standards from oncology into the autoimmune disease setting, where clinical contexts, risk profiles, and patient needs differ substantially.

How can or should an institution prepare or assess its preparedness for CAR trials?

Caricchio and Sheikh: Preparation starts with an honest assessment of institutional infrastructure and clinical workflows. Centers should ensure access to essential resources, including apheresis, inpatient monitoring, ICU support, pharmacy expertise, and clinical and research teams experienced in recognizing and managing CAR T-related toxicities.

Institutions also need standardized clinical pathways for complications such as cytokine release syndrome, neurotoxicity, cytopenias, infections, and autoimmune disease-specific issues. From a clinical trial perspective, it is important to confirm an adequate referral base and the ability to support long-term follow-up, as these patients require prolonged safety monitoring.

The key takeaway is that successful CAR T-cell clinical trials in autoimmune disease require more than enthusiasm. Centers must have the right infrastructure, expertise, and long-term support systems in place before they are ready to enroll patients.

Generally speaking, what are some key improvement opportunities for facilities in this area?

Caricchio and Sheikh: One key opportunity is stronger integration between rheumatology, hematology/cellular therapy, nephrology, and other relevant subspecialty teams. Clear communication, shared protocols, and defined roles across disciplines can significantly improve both safety and operational efficiency, particularly for patients with multisystem disease involvement. Another important area is staff education and training, especially for clinicians and nurses who may not routinely care for CAR T-treated patients. Early symptom recognition and well-defined escalation pathways are essential. Many centers can strengthen their long-term follow-up infrastructure, including surveillance for infections and secondary malignancies, as well as systematic collection of patient-reported outcomes.

Successful expansion of CAR T-cell therapy into autoimmune disease requires coordinated, multispecialty collaboration, focused staff training, and robust systems for long-term patient monitoring.

What is your bottom-line message to clinicians and researchers?

Caricchio and Sheikh: CAR T-cell therapy has the potential to transform treatment for severe autoimmune diseases, but it is not a “plug-and-play” intervention. Early clinical outcomes are encouraging, yet success hinges on careful planning, multidisciplinary collaboration, and disciplined clinical oversight.

For clinicians and researchers, the key message is that enthusiasm for innovation must be matched by rigorous execution. Patient safety and long-term outcomes depend on it.

Read the study here and expert commentary on the clinical implications here.

by Scott Harris, Contributing Writer, MedPage Today | January 5, 2026 

Sheikh reported receiving financial support from Aurinia Pharmaceuticals, Pfizer, GlaxoSmithKline, AstraZeneca, Genentech, and Biogen. Caricchio reported financial support from LRA/LUCIN, Cabaletta, Nkarta, Kyverna, and BMS.Primary SourceACR Open RheumatologySource Reference: Caricchio R, et al “A guide for initiating and managing chimeric antigen receptor T cell therapy clinical trials in autoimmune rheumatic diseases” ACR Open Rheumatol 2025; DOI: 10.1002/acr2.70139.