Re-establishing immune tolerance against multiple ? cell antigens using novel epitope delivery approaches

The incidence of Type 1 diabetes (T1D) has been steadily increasing and about 1.25 million Americans are living with T1D. The disease can only be managed by insulin injection, but not cured, and many patients remain prone to developing long-term complications. There is no optimum therapy for T1D and effective therapies have mostly depended on strategies that induce non-specific immune suppression, resulting in severe side effects. More specific therapies like antigen-specific immunotherapies which aim at inducing tolerance to the beta cell antigens that otherwise stimulate the disease-causing T cells are safe but showed poor efficacy in clinical trials. Insufficient antigen representation and inadequate antigen delivery may have contributed to the poor efficacy of these therapies. Therefore, novel approaches will be used to efficiently deliver multiple epitopes (antigen fragments that are actually recognized by the T cells) in two forms: 1) attached to a molecule that facilitates their uptake by cells and 2) produced inside cells from RNA genetic instructions introduced by nanoparticle carriers. Both approaches combine aspects of nanomedicine (use of tiny particles that improve transport, stability and uptake by target cells) and precision medicine (use of customizable population-specific epitopes). The feasibility of these approaches including targeting additional types of antigen-presenting cells of therapeutic interest has been demonstrated in mouse models of T1D. These strategies only affect the specific T cells that need to be reprogrammed to protect from rather than contribute to T1D. These promising approaches are anticipated to enhance the efficacy of immunotherapy for T1D patients in the future.