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Proinsulin peptide-pulsed tolerogenic dendritic cells represent an autologous cell therapy approach designed to restore immune tolerance in patients with Type 1 Diabetes Mellitus. This therapy involves the *ex vivo* differentiation of a patient's own monocytes into dendritic cells, which are then treated with immunosuppressive agents—typically Vitamin D3 and dexamethasone—to induce a stable tolerogenic phenotype (tolDCs). These cells are subsequently loaded, or 'pulsed,' with specific proinsulin peptides, such as the proinsulin signal peptide. When re-administered to the patient, usually via intradermal injection, these tolDCs migrate to the lymph nodes and present the proinsulin antigen to T-cells in the absence of co-stimulatory signals. This antigen-specific presentation induces the expansion of regulatory T-cells (Tregs) and promotes T-cell anergy or deletion, thereby specifically dampening the autoimmune attack on pancreatic beta-cells while leaving the rest of the immune system intact. This candidate has been primarily developed and investigated by the Leiden University Medical Center (LUMC).
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