Late-breaking: Myelin-peptide coupled red blood cells

Induction of antigen-specific immune tolerance is a promising therapeutic approach in autoimmune diseases. Peptide-coupled cell tolerance is effective in several animal models of autoimmune disease, allergies and transplantation. Prof. Andreas Lutterotti (University of Zurich, Switzerland) and colleagues developed a therapeutic regimen employing autologous blood cells, chemically coupled with 7 myelin peptides, to induce antigen-specific tolerance in MS patients [1].

After a successful trial with myelin peptide-coupled peripheral blood mononuclear cells (PBMCs) in MS patients, the researchers optimised the approach using red blood cells (RBCs) as tolerogenic carriers (see Figure) [2]. ETIMS^red is the first-in-human phase 1b trial, to test the safety and tolerability of increasing doses of autologous peptide-coupled RBCs. Ten relapsing-remitting MS patients (mean age 38.5; 70% female) were treated with increasing doses of peptide-coupled RBCs.

Figure. Tolerance induction with peptide-coupled RBCs or white blood cells [2]



The trial met its primary endpoint, demonstrating feasibility, safety, and excellent tolerability. There were no adverse events within the 24 hours after infusion and no serious adverse events occurred in the trial. Patients remained stable in all clinical parameters. The trial was accompanied by mechanistic studies to assess in vivo immunological effects of the therapy [2]. Frequency of myelin peptide-specific T cells reduced after tolerization (more pronounced in high-dose patients), which suggests there was antigen-specific tolerization. Increases in regulatory T cells and IL-10, as well as a reduction of neurofilament light chain, point towards active mechanisms of immune tolerance [2]. The next step is to expand the peptide cocktail to novel antigens. A phase 2a trial to assess the efficacy of the approach is being developed.

1. Turley DM, Miller SD. J Immunol. 2007;178:2212-20.
2. Lutterotti A, et al. ECTRIMS 2019, abstract 339.

Posted on 8 November, 201918 March, 2024