Induction of antigenic immune tolerance to delay type 1 diabetes - challenges for clinical translation

• Published in: Current opinion in endocrinology, diabetes, and obesity Vol. 29; no. 4; p. 379
• Main Authors: Wesley, Johnna D, Pagni, Philippe P, Bergholdt, Regine, Kreiner, Frederik Flindt, von Herrath, Matthias
• Format: Journal Article
• Language: English
• Published: England 01.08.2022
• Subjects: Autoantigens; Diabetes Mellitus, Type 1; Humans; Immune Tolerance; Immunotherapy - methods; Insulin-Secreting Cells
• ISSN: 1752-2978
• DOI: 10.1097/MED.0000000000000742

Dissect the field of antigen-specific immunotherapy (ASIT) in type 1 diabetes (T1D), highlighting the major barriers currently blocking clinical translation. ASIT remains a promising approach in T1D to re-establish the proper balance in the immune system to avoid the autoimmune-mediated attack or destruction of beta-cells in the pancreas. Despite some encouraging preclinical results, ASIT has not yet successfully translated into clinical utility, predominantly due to the lack of validated and clinically useful biomarkers. To restore immune tolerance towards self-antigens, ASIT aims to establish a favourable balance between T effector cells and T regulatory cells. Whilst most ASITs, including systemic or oral administration of relevant antigens, have appeared safe in T1D, meaningful and durable preservation of functional beta-cell mass has not been proven clinically. Development, including clinical translation, remains negatively impacted by lack of predictive biomarkers with confirmed correlation between assay readout and clinical outcomes. To be able to address the high unmet medical need in T1D, we propose continued reinforced research to identify such biomarkers, as well efforts to ensure alignment in terms of trial design and conduct.