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**Proinsulin peptide-loaded tolerogenic dendritic cells** (also known as **PIpepTolDC**) is an investigational autologous cell-based immunotherapy developed by the Leiden University Medical Center (LUMC) and also evaluated by the City of Hope Medical Center for the treatment of type 1 diabetes mellitus (T1D). The therapy consists of autologous tolerogenic dendritic cells (tolDCs) generated ex vivo from patient-derived monocytes using a combination of vitamin D3 and dexamethasone. These cells are subsequently loaded (pulsed) with the specific proinsulin peptide C19-A3. Upon intradermal administration, these tolDCs present the proinsulin antigen to the host immune system in a tolerogenic context, aiming to suppress the autoimmune destruction of pancreatic beta cells by inducing antigen-specific regulatory T cells (Tregs) and reducing the autoreactive T-cell response. The therapy has been evaluated in Phase 1 clinical trials (including the 'D-Sense' trial), demonstrating safety, feasibility, and a durable reduction in autoimmune T-cell responses.
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