Antigen-Specific Immune Tolerance in Multiple Sclerosis-Promising Approaches and How to Bring Them to Patients.

Andreas Lutterotti,Roland Martin,Helen Hayward-Koennecke,Mireia Sospedra

doi:10.3389/fimmu.2021.640935

Andreas Lutterotti, Roland Martin + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2021.640935

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Abstract

Antigen-specific tolerance induction aims at treating multiple sclerosis (MS) at the root of its pathogenesis and has the prospect of personalization. Several promising tolerization approaches using different technologies and modes of action have already advanced to clinical testing. The prerequisites for successful tolerance induction include the knowledge of target antigens, core pathomechanisms, and how to pursue a clinical development path that is distinct from conventional drug development. Key aspects including patient selection, outcome measures, demonstrating the mechanisms of action as well as the positioning in the rapidly growing spectrum of MS treatments have to be considered to bring this therapy to patients.

Highlights

Therapeutic interventions in medicine should provide the highest possible specificity and wellknown mechanisms when targeting the pathogenic processes underlying a specific disease
The concept of reverting autoimmunity by induction of antigen-specific immune tolerance stands in contrast to currently available therapies, which target the inflammatory immune response broadly, often compromise protection against infections and may even lead to secondary autoimmunity
A randomized, placebocontrolled clinical trial in early relapsing-remitting multiple sclerosis (MS) (RRMS) patients failed the primary endpoint of reducing clinical disease activity, including the number of relapses and disability progression, despite promising data on antigen-specific T cells [47]

Summary

Introduction

Therapeutic interventions in medicine should provide the highest possible specificity and wellknown mechanisms when targeting the pathogenic processes underlying a specific disease. A randomized, placebocontrolled clinical trial in early relapsing-remitting MS (RRMS) patients failed the primary endpoint of reducing clinical disease activity, including the number of relapses and disability progression, despite promising data on antigen-specific T cells [47].

Results

Conclusion