Phase 1 Trial Demonstrates Antigen-Specific Treg Induction via Peptide-Coupled Red Blood Cells in MS

The open-label study enrolled nine patients with relapsing-remitting MS and administered a single intravenous dose of peptide-coupled erythrocytes. Peripheral blood was monitored for changes in T-cell phenotype and function over 12 weeks. No serious adverse events occurred; infusion reactions were mild and transient. Flow cytometry and ELISPOT assays showed expansion of myelin-reactive FoxP3+ Tregs and reduced Th1/Th17 responses to the targeted antigens, while responses to unrelated antigens remained intact.

Existing MS therapies such as natalizumab or ocrelizumab reduce inflammatory activity but impair host defense against infection and malignancy. This approach exploits natural clearance of erythrocytes in the liver and spleen to deliver antigen in a tolerogenic context, a strategy previously validated in mouse EAE models but not previously tested in humans. The trial therefore provides the first direct evidence that erythrocyte-coupled antigens can shift the human T-cell repertoire toward regulation without measurable lymphopenia or hypogammaglobulinemia.

The investigators have formed Cellerys to advance the program. A randomized, placebo-controlled phase 2 study is planned once financing is secured; primary endpoints will include gadolinium-enhancing lesions on MRI and clinical relapse rate at 24 weeks. Key open questions include durability of tolerance after repeated dosing and whether the same platform can be applied to other organ-specific autoimmune diseases.