Jeniffer D Loaiza Naranjo1, Anne-Sophie Bergot1, Irina Buckle2, Emma E Hamilton-Williams3. 1. The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia. 2. Mater Research Institute UQ, The University of Queensland, Woolloongabba, QLD, 4102, Australia. 3. The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia. e.hamiltonwilliams@uq.edu.au.
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.
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 humanproinsulin 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.
Entities:
Keywords:
Antigen-specific immunotherapy; Islet epitopes; Nanotechnology; T cell tolerance; Type 1 diabetes