Treatment of multiple sclerosis with peptide-coupled red blood cells induces antigen-specific T regulatory cells.

Authors

Andreas Lutterotti, Thomas Ludersdorfer, María José Docampo, Muriel Morax, Helen Hayward-Koennecke, Pietro Oldrati, Vasileia Kalaitzaki, Zoe Marti, Angela Zaugg, Mattias Bronge, Olivia G Thomas, Filipa Marques Ferreira, Carla Sellés Moreno, Carolina Cruciani, Reza Naghavian, Jacobo Sarabia Del Castillo, Laure Tillé, Markus Reindl, Pavlos C Englezou, René Stenger, Ilijas Jelcic, Nikolai Pfender, Marc Hilty, Magdalena Foege, Federica Guffanti, Verena Weichselbaumer, Alain Blanc, Thorsten Buch, Martin Hüllner, Sebastian Winklhofer, Valerie Treyer, Jeroen S Goede, Martin Behe, Massimo Broggini, Eugenio Scanziani, Tomas Olsson, Hans Grönlund, Maria Pia Sormani, Martin Kayser, Mireia Sospedra, Roland Martin

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 36. Pages e2614908123. Sep 08, 2026. Epub Aug 31, 2026.

Abstract

Inducing antigen-specific immune tolerance is a long-standing aim in organ-specific autoimmune diseases including multiple sclerosis (MS). We developed a therapy based on autologous red blood cells (RBCs) as tolerizing carriers of autoantigens and tested these in an open-label, dose-escalation, phase Ib clinical trial with clinical, imaging, and mechanistic readouts. RBCs coupled with seven immunodominant myelin peptides (pcRBCs) were safe and well tolerated. Several clinical and imaging readouts remained stable, which was supported by a reduction of neurofilament light chain indicating reduced tissue inflammation in the brain. Single-cell RNA sequencing identified expansion of antigen-specific CD4+ memory T cells with regulatory phenotypes and loss of proinflammatory cells three months after a single administration of pcRBCs. This was corroborated by a reduction of autoreactive CD4+ T cell responses and an early increase of IL-10, Tr1 regulatory T cells and tolerogenic monocytes and plasmacytoid dendritic cells. Biodistribution studies in mice and humans demonstrate that pcRBCs are rapidly processed by Kupffer cells in the liver and by marginal zone macrophages in the spleen. In summary, pcRBCs are a promising autologous cell therapy for achieving antigen-specific immune tolerance in MS.

PMID:
42673466
Bibliographic data and abstract were imported from PubMed on 01 Sep 2026.

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