A Question of Tolerance-Antigen-Specific Immunotherapy for Type 1 Diabetes.

ABSTRACT

PURPOSE OF REVIEW Antigen-specific immunotherapy (ASI) is a long sought-after goal for type 1 diabetes (T1D), with the potential of greater long-term safety than non-specific immunotherapy. We review the most recent advances in identification of target islet epitopes, delivery platforms and the ongoing challenges. RECENT FINDINGS: It is now recognised that human proinsulin contains a hotspot of epitopes targeted in people with T1D. Beta-cell neoantigens are also under investigation as ASI target epitopes. Consideration of the predicted HLA-specificity of the target antigen for subject selection is now being incorporated into trial design. Cell-free ASI approaches delivering antigen with or without additional immunomodulatory agents can induce antigen-specific regulatory T cell responses, including in patients and many novel nanoparticle-based platforms are under development. ASI for T1D is rapidly advancing with a number of modalities currently being trialled in patients and many more under development in preclinical models.