Autoimmune diseases usually require long-term treatment. Doctors who treat these diseases have dreamed of a time-limited treatment that can reduce the use of immunosuppressive drugs and decrease toxicities.

During the session Welcome Awards & Plenary: Transplantation and Cell Therapy for Autoimmune Disorders, three experts discussed the progress to date in transplantation and cellular therapy for the long-term control of autoimmune diseases.

Since 2011, three randomized trials have been conducted comparing hematopoietic stem cell transplantation (HSCT) to cyclophosphamide for systemic sclerosis (SSc), all of which have demonstrated superior outcomes with HSCT. This progress has led to the possibility of discussing a cure with these patients, said Keith Sullivan, MD, professor of medicine at Duke University Medical Center.

“Patients 10 years after transplant for SSc who are in remission and off DMARDs (disease-modifying antirheumatic drugs) view themselves as cured,” he said.

Sullivan offered advice on performing HSCT. First, he recommended that patients be enrolled in clinical trials if available. He emphasized the importance of performing transplants at experienced centers with established collaborations, as data has shown better outcomes at these facilities. Further, he highlighted that transplants should be performed early during the disease. In deciding between allogeneic and autologous HSCT, he highlighted that evidence favors autologous transplantations in adults. Most importantly, he said these patients should be monitored for life-long toxicity and relapse by a multidisciplinary team.

Georg Schett, MD, head of the Department of Medicine 3 – Rheumatology and Immunology at Uniklinikum Erlangen and vice president of research at Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany, presented data on chimeric antigen receptor (CAR) T-cell therapy for autoimmune diseases.

Over the last 20 years, the understanding of the pathophysiology of autoimmune diseases has improved, and this progress led to the development of therapies aimed at depleting B cells, like rituximab. However, rituximab has limited efficacy for some autoimmune diseases, potentially because it is a poor depleter of tissue B cells.

CAR T-cell therapy takes a fundamentally different approach to targeting these cells for three reasons, Schett explained. First, CAR T cells act as a living drug, and they have an almost proliferative capacity in-vivo upon antigen engagement, allowing for better depletion efficacy. Second, they are serial killers, and third, they effectively penetrate tissues.

Schett presented results from 15 patients with autoimmune diseases treated with CD19 CAR T-cell therapy at his center. All but one of these patients could completely stop immunosuppressive and glucocorticoid therapy.

“It was very interesting that the disease didn’t come back, and we think that this can be described like a deep, narrow valley,” Schett said.

Within seven days, the B cells disappeared in these patients, reappearing between 50 and 150 days later. When the B cells reconstituted, they were naive. There were very few memory B cells, low levels of plasmablasts, and minimal levels of activated memory B cells in patients treated with CD19 CAR T-cell therapy. Additionally, B cells were completely absent from the lymph nodes, and follicular structures were eliminated.

Sonali Bracken, MD, PhD, fellow in the division of rheumatology at Duke University, discussed the immunopathogenesis of human autoimmune disease and the role of targeting B cells in systemic lupus erythematosus.

“The rationale behind targeting B cells with drugs like CD19 CAR T cells is because B cells exert a variety of effector functions that contribute to the pathogenesis of autoimmunity,” Bracken said.

B cell subsets can be targeted along various developmental stages based on the pattern of surface markers they express. Until now, B-cell-targeted monoclonal therapies have focused on the CD20 antigen. However, CD19 is expressed on a broader array of B cells.

Bracken highlighted why she thinks CD19 CAR T-cell therapies are effective in patients with lupus and other autoimmune diseases. While rituximab and CD19 CAR T-cell therapy were equally effective at depleting peripheral B cells, there was a difference at the tissue level. Patients who received CD19 CAR T-cell therapy had a complete depletion of tissue-resonant B cells that was not seen after rituximab.

Deep B cell depletion with CAR T-cell therapy offers hope for drug-free disease remission in patients with autoimmune diseases. Further, it may help reduce these patients’ pill burden through its downstream effects on other pathogenic pathways.

This and other sessions at the 2025 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT® and CIBMTR® will be available for on-demand viewing for registered attendees following the live presentation.