What’s Hot in 2025: Autoimmune Diseases

101 uses for B cell-depletion therapy in certain subsets of the autoimmune population

Riding on the coattails of the tremendous success of cell therapies and biologics in oncology—many of the forerunners of which were developed to treat B cell-associated cancers—experts in the field have sought to extend use of these therapeutics into autoimmune indications where there is an established B cell pathophysiology. This offers considerable benefit due to the known safety profile, albeit with a disparate patient subset. Ocrelizumab (Roche), a monoclonal antibody approved by the FDA in 2017, has been available to multiple sclerosis patients for some time now, and in 2024, a bispecific T cell engager, Blinatumomab (Amgen), has been used to successfully treat systemic sclerosis and rheumatoid arthritis patients in early phase clinical trials. Cabaletta Bio (CABA-201) in 2024 reported impressive early data in lupus trials with their CD19-CAR-T therapeutic, and there is growing interest in the autoimmune disease area with an associated healthy compound annual growth rate.

Preclinical screens using primary human immune cell models to assess both efficacy and safety of B cell- depleting therapeutics can be challenging due to B cell paucity in peripheral blood, particularly of rare autoreactive plasma cells which reside in the bone marrow niche. Fortunately, headway is being made and tonsil organoids (Wagar et al, 2021) are being used to address some of these questions with greater representation of a wider range of B cell subsets to aid understanding of therapeutic selectivity, whilst also providing effector cells (NK or T cells) to support assessment of B cell depletion. 

Next-generation mouse models

Autoimmune models to support development of advanced modalities have long been an unmet need and as the market continues to grow, will become increasingly necessary. Past efforts have been beset by an imperfect understanding of the aetiology of many autoimmune diseases and a requirement for human major histocompatibility complex (MHC) expression to support disease development. However, with advancement of next-generation mice, supporting broader and prolonged immune cell engraftment, or even more recently of the THX mouse (Chupp et al, 2024), which sports a broad human immune repertoire and can develop a lupus-like disease, the future feels closer than ever.  

—Louise Brackenbury, PhD, Science Director, Advanced Modalities, Charles River