Author Of 1 Presentation

Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0356 - MOG-derived Imotopes, a new class of MHC-II epitope modification, inducing cytolytic CD4 T-cells as novel immunotherapy in multiple sclerosis          (ID 1280)

Speakers
Presentation Number
P0356
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

ImotopesTM are synthetic peptides comprising an MHC-II T cell epitope sequence of an autoantigen associated in its flanking region with an amino acid motif having a thiol-disulfide oxidoreductase activity. Specific stimulation of CD4+ T cells with their cognate ImotopeTM can elicit cytolytic CD4+ T cells (cCD4) which are able to induce apoptosis of antigen presenting cells (APCs) presenting said T cell epitopes and also to eliminate pathogenic T cells activated by other epitopes on the same APC (bystander effect). Hence, ImotopesTM treatment has the potential to specifically eliminate pathogenic auto-immune responses and to possibly cure auto-immune diseases like multiple sclerosis.

Objectives

This study aimed to develop an ImotopeTM comprising an MHC-II T cell epitope contained within the MOG autoantigen, and to demonstrate its potency to generate in vitro specific and cytolytic CD4+ T cells from MS patients PBMCs.

Methods

MS patients PBMCs were used as a source of naïve CD4+ T cells. These were co-cultured with autologous APCs loaded with the ImotopeTM and periodically re-stimulated. ImotopeTM ability to generate antigen specific CD4+ T cells was evaluated by flow cytometry analysis and quantification of cytokines secretion in cells culture supernatants. Moreover, the lytic activity of the induced CD4+ T cells was evaluated by APC apoptosis quantification upon cognate interaction.

Results

ImotopeTM-induced CD4+ T cell lines were generated from several MS patients (n=6). Upon ImotopeTM re-stimulation, their specificity was detected by upregulation of the activation marker CD154 and by cytokines release, like for example IL-5. Furthermore, ImotopeTM-specific CD4+ T cell lines were reactive to the wild type T cell epitope, confirming their capacity to respond to the natural autoantigen. Importantly, ImotopeTM-induced CD4+ T cell lines were able to drive ImotopeTM-loaded APCs into apoptosis demonstrating their cytolytic phenotype.

Conclusions

The MOG-derived ImotopeTM designed to treat MS patients is able to induce autoantigen specific CD4+ T cells with a cytolytic phenotype (cCD4). This opens new avenues for therapeutic intervention with curative potential in MS.

Collapse