O03 The efficacy and immunomodulatory effects of umbilical cord-derived mesenchymal stromal cells (UC-MSCs) for severe, biologic therapy-refractory psoriasis

Abstract Introduction and aims Biologic therapies have transformed the treatment of moderate-to-severe psoriasis. However, disease management remains challenging for patients who have failed all available treatments. Mesenchymal stromal cells (MSCs) are immunomodulatory and show promise for treating immune-mediated inflammatory diseases. We investigated the efficacy and safety of allogeneic umbilical cord-derived MSCs (UC-MSCs) for treating severe, biologic-refractory psoriasis and their modulatory effects on peripheral blood mononuclear cells (PBMCs) in a compassionate use study. Methods Three women (aged 44, 45 and 46 years) with severe plaque psoriasis who had failed at least five biologics across four classes were administered two infusions of UC-MSCs (1.5–3 × 106 cells per kg) a week (W) apart, either as monotherapy (two cases) or adjuvant therapy with etanercept biosimilar. Clinical efficacy was measured by Psoriasis Area and Severity Index (PASI). PBMCs were isolated before and up to W6–W35 after UC-MSCs infusion, and subjected to deep immunophenotyping using multiparameter flow cytometry. Results UC-MSCs improved the clinical severity of psoriasis from 39–87% (PASI 39–87). Upon eventual relapse of psoriasis post-UC-MSCs, two patients recommenced a previously failed biologic (guselkumab and bimekizumab) at W9; both had a greater and sustained response than previously, achieving PASI 94 and PASI 96 respectively, for > 12 months from biologic reinitiation. Increased frequency of CD4+ and CD8+ recirculating (CLA+CD103+) and skin-homing (CLA+CD103−) T cells, and CD25HiCD127LoFOXP3+ regulatory T cells (Tregs) in peripheral blood were observed in all patients following UC-MSCs and biologic reinitiation; these were associated with clinical improvement. Notably, all patients exhibited at least twofold increase in Tregs following either UC-MSCs or biologic reinitiation. Conclusions UC-MSC treatment ameliorated severe psoriasis and enhanced responsiveness to previously failed biologics. These clinical data, coupled with changes in circulating immune cells, implicate a resetting of the peripheral T-cell immune compartment. Further studies are required to investigate efficacy, and elucidate the immunomodulatory mechanism of action of MSCs in severe psoriasis.