Antigen-based immune modulation therapy for type 1 diabetes: the era of precision medicine.

Precision medicine has emerged as a mantra for therapeutic approaches to complex diseases. The defining concept relies on a detailed insight into disease pathogenesis and therapeutic mechanism. Although the type 1 diabetes field has gained new insights into disease endotypes and indications of efficacy for several therapies, none of these is yet licensed, partly because of immune suppressive side-effects beyond control of islet autoimmunity. New strategies designed to regulate the immune system continue to emerge as basic science discoveries are made, including the use of antigen-based immunotherapies. A single agent or approach seems unlikely to halt disease progression in all people with or at risk of type 1 diabetes; as such, tailored methods relying on patient subgroups and knowledge of disease endotypes are gaining attention. Recent insights into disease mechanisms and emerging trial data are being translated into opportunities for tissue-specific prevention of progressive loss of β-cell function and survival. Results so far point to feasibility, safety, and tolerability of administration of islet autoantigens and peptides thereof into recipients with or at risk of type 1 diabetes. Findings from mechanistic studies suggest favourable changes in islet autoimmunity, with signs of immune regulation. Major challenges remain, including those related to dose and dosing frequency, route of administration, and use of adjuvants. However, the first steps towards tissue-specific and personalised medicine in type 1 diabetes have been made, which will guide future studies into induction of immune tolerance to intervene in the initiation and progression of islet autoimmunity and disease.

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