A century later, still fighting back: antigen-specific immunotherapies for type 1 diabetes


Por: Rodriguez-Fernandez, S, Almenara-Fuentes, L, Perna-Barrull, D, Barneda, B and Vives-Pi, M

Publicada: 1 may 2021 Ahead of Print: 1 feb 2021
Resumen:
Type 1 diabetes (T1D) is a chronic metabolic disease caused by the autoimmune destruction of insulin-producing beta-cells. Ever since the 1920s, the fate of patients suffering from T1D was dramatically improved owing to the isolation and production of insulin, and the scientific field has largely progressed as a result of the evidence gathered about its underpinnings and mechanisms. The last years have seen this knowledge transformed into actual antigen-specific immunotherapies with potential to restore selectively the breach of tolerance to beta-cell autoantigens and halt the autoimmune aggression. However, so far, the results of both prevention and reversion trials in T1D have been rather discouraging, so there is still an urgent need to optimize those immunotherapies and their associated factors, for example, posology and administration patterns, route and timing. In this review, we look back on what has been achieved in the last century and identify the main autoantigens driving the autoimmune attack in T1D. Then, we take a deep dive into the numerous antigen-specific immunotherapies trialed and the ones still at a preclinical phase, ranging from peptides, proteins and agent combinations to gene transfer, nanoparticles, cell-based strategies and novel approaches exploiting naturally occurring tolerogenic processes. Finally, we provide insight into the several features to be considered in a T1D clinical trial, the ideal time point for intervention and the biomarkers needed for monitoring the successful regulatory effect of the antigen-specific immunotherapy. Although further research and optimization remain imperative, the development of a therapeutic armamentarium against T1D autoimmunity is certainly advancing with a confident step.

Filiaciones:
:
 Autonomous Univ Barcelona, Germans Trias I Pujol Res Inst, Immunol Sect, Badalona, Spain

 Ahead Therapeut SL, Barcelona, Spain

Almenara-Fuentes, L:
 Autonomous Univ Barcelona, Germans Trias I Pujol Res Inst, Immunol Sect, Badalona, Spain

 Ahead Therapeut SL, Barcelona, Spain

:
 Autonomous Univ Barcelona, Germans Trias I Pujol Res Inst, Immunol Sect, Badalona, Spain

Barneda, B:
 Ahead Therapeut SL, Barcelona, Spain

:
 Autonomous Univ Barcelona, Germans Trias I Pujol Res Inst, Immunol Sect, Badalona, Spain

 Ahead Therapeut SL, Barcelona, Spain
ISSN: 08189641





Immunology and Cell Biology
Editorial
Springer Verlag, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Alemania
Tipo de documento: Review
Volumen: 99 Número: 5
Páginas: 461-474
WOS Id: 000616776400001
ID de PubMed: 33483995
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