#3-39E. The Dawn of Off-the-Shelf Immune Reset Therapies (NatRevRheumatol, 2025)

Are we witnessing the end of logistical barriers in cellular therapy for refractory autoimmune diseases? This year-in-review article highlights the pivotal 2025 shift toward "off-the-shelf" B cell-depleting modalities, including allogeneic cellular products, in vivo CAR engineering via lipid nanoparticles, and bispecific T cell engagers. These innovations aim to circumvent the high costs and manufacturing complexities of autologous CAR-T therapy while maintaining the potential for durable, drug-free remission. The most critical clinical insight is that these universal agents—such as allogeneic CD19-targeted T cells and iPSC-derived CAR-NK cells—have demonstrated efficacy comparable to autologous approaches in severe systemic lupus erythematosus and systemic sclerosis3.** However, physicians must critically interpret these findings with caution; while accessibility is improved, significant safety signals such as cytokine release syndrome and liver toxicity were observed, necessitating further optimization of toxicity profiles.** For the practicing clinician, this paper signals a transformative era where potent immune-resetting therapies could evolve from niche procedures into scalable, ready-to-use treatments for difficult-to-treat autoimmune conditions.

Citation: Xu, H. The dawn of ‘off-the-shelf’ B cell-depleting therapies for autoimmune diseases. Nature Reviews Rheumatology. 2025. DOI: 10.1038/s41584-025-01343-5

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