CAR T-Cell Therapy Shows Promise in Treating Autoimmune Diseases: Clinical Trials and Future Directions
Key Insights
UChicago Medicine launched a Phase 2 clinical trial to explore CAR T-cell therapy for systemic lupus erythematosus (search), inflammatory myositis (search), and systemic sclerosis (search).
CAR T-cell therapy, initially for blood cancers, is being adapted to autoimmune diseases, potentially offering a new solution for resistant cases.
BMS reported promising Phase 1 trial results using CD19 (search) CAR T-cells for severe autoimmune diseases, showing significant disease activity reduction.
The University of Chicago Medicine is spearheading a Phase 2 clinical trial to investigate the use of CAR T-cell therapy in treating autoimmune diseases, marking a significant expansion from its traditional application in oncology. This trial focuses on systemic lupus erythematosus (search), inflammatory myositis (search), and systemic sclerosis (search), offering hope for patients with conditions resistant to standard therapies. CAR T-cell therapy, first approved by the FDA in 2017 for certain B-cell lymphomas, involves modifying a patient's T cells to target specific disease-contributing cells.
Expanding CAR T-Cell Therapy Beyond Oncology
Satyajit Kosuri, MD, Assistant Professor of Medicine at UChicago Medicine, highlighted the potential of CAR T-cell therapy beyond oncology, noting its adaptability to areas like rheumatology and neurology. The current standard treatment for autoimmune diseases often involves glucocorticoids and other medications, which can have significant side effects and may not always prevent disease flares. Iazsmin Bauer Ventura, MD, a rheumatologist at UChicago Medicine, referenced a New England Journal of Medicine study that evaluated CAR T-cell therapy in 15 patients with similar autoimmune diseases, finding it feasible, safe, and efficacious, thus warranting further controlled trials.
Clinical Trial Details and Patient Considerations
The UChicago Medicine trial includes a detailed screening process to ensure patient suitability, with participants undergoing comprehensive testing. Patients receive a mild chemotherapy regimen to prepare their bodies for the engineered CAR T cells and are typically hospitalized for four to seven days. UChicago Medicine is one of nine sites for this trial, sponsored by Cabaletta (search), which specializes in CAR T-cells for rheumatologic diagnoses. The trial is open to adults aged 18 to 75, with a juvenile protocol for patients under 18 with dermatomyositis (search).
BMS's Advancements in CAR T-Cell Therapy for Autoimmune Diseases
Bristol Myers Squibb (search) (BMS) is also making strides in this area, with Tim Campbell, Vice President of Hematology and Cell Therapy, Early Clinical Development at BMS, expressing optimism about their CAR T-cell therapy's potential to transform the underlying disease. BMS's CAR T-cell therapy, CC-97540 (BMS-986353), utilizes the same CD19 (search) construct as Breyanzi, their FDA-approved therapy for certain leukemia and lymphoma patients, but with a shorter manufacturing process. Early results from their Phase 1 trial, involving patients with lupus (search), scleroderma (search), and inflammatory myositis (search), have shown transformational efficacy, with patients coming off immunosuppressive medications and experiencing significant reductions in disease activity scores.
Safety and Future Directions
While CAR T-cell therapy is generally considered safe, some patients have experienced side effects like neurologic toxicities or cytokine release syndrome. However, recent advancements in managing these side effects and the differences between blood cancers and autoimmune diseases give researchers hope for fewer side effects in autoimmune disease trials. Aimee Payne, MD, PhD, at Columbia University, is focusing on making CAR T-cell therapy more precise to avoid the permanent loss of B-cells, while Joseph R. Arron, MD, PhD, at Sonoma Biotherapeutics, is exploring regulatory T cells (Tregs) to promote immune homeostasis and tissue repair. Atara Biotherapeutics is also advancing allogeneic T cell platforms for both oncology and autoimmune treatments, aiming to address the scalability challenges of autologous CAR T-cell therapies.
The Broader Landscape of CAR T-Cell Therapy in Autoimmune Disease
Companies like Kyverna Therapeutics, Cabaletta (search) Bio, and Cartesian Therapeutics are also leading the charge, with cell therapies in Phase 2 trials for autoimmune diseases. Experts emphasize the need for long-term data and caution against overhyping the therapy, acknowledging that it may not be curative for all patients. The Lupus (search) Research Alliance and Lupus Therapeutics are key players in facilitating research in this space, emphasizing the importance of translating learnings from oncology to rheumatology and supporting patient education. As the field progresses, there is a growing focus on optimizing safety, efficacy, and accessibility, as well as exploring the potential of using CAR T-cell therapy earlier in the treatment course to prevent organ damage.