OP0097 PROOF-OF-CONCEPT OF FIBROBLAST-TARGETED PHOTODYNAMIC THERAPY IN HUMAN 3D SCLERODERMA SKIN MODEL AND BLEOMYCIN-INDUCED SKIN FIBROSIS IN MICE

Background Systemic sclerosis (SSc) is a rare, severe auto-immune disease characterized by inflammation, vasculopathy and fibrosis. Activated (myo)fibroblasts are crucial drivers of By exploiting their expression fibroblast activation protein (FAP) to perform targeted photodynamic therapy (tPDT), we can locoregionally deplete these pathogenic cells. Objectives We explored the use FAP-tPDT selectively target primary skin fibroblasts from SSc patients, both in 2D 3D cultures, as well biopsies fibrotic lesions murine bleomycin-induced fibrosis model. Methods The FAP targeting monoclonal antibody (clone 28H1) was conjugated with photosensitizer IRDye700DX. Primary were obtained lesional patients via spontaneous out-growth subsequently cultured on plastic or collagen type I. For FAP-tPDT, cells incubated buffer without antibody-photosensitizer (Ab-PS) construct, washed after 4 h exposed λ = 689 nm light (50 J/cm 2 at 280 mW/cm ). Cell viability measured using CellTiter Glo. seeded plugs underwent same treatment procedure. Contraction followed over time determine myofibroblast activity. Skin induced mice 3x/week injections 1.5 IU bleomycin intradermally back mouse. After 5 weeks sacrificed taken affected not skin. These Ab-PS construct control Ab-PS. washing, light, for 1h formalin fixed paraffin embedded. Sections immuno stained presence cleaved caspase-3. Results resulted antibody-dose dependent cytotoxicity upon exposure. Cells did show this response. fully prevented contraction fibroblasts. Even incubation very low dose (0.4 nM) inhibited out 3 donors. In fibrosis, an upregulation apoptosis, evidenced increased caspase-3 staining (Figure 1), observed response FAP-tPDT. increase staining, nor alone. Figure 1. Cleaved dermal red arrows indicate positive Conclusion Here have shown, first time, potential selective relevant patient-derived culture models vivo model Disclosure Interests Daphne Dorst: None declared, Arjan van Caam: Elly Vitters: Birgitte Walgreen: Monique Helsen: Christian Klein Employee of: CK employee Roche pharmaceutics, Shreya Gudi: Tirza Wubs: Jyoti Kumari: Przemysław Błyszczuk: Madelon Vonk: Peter der Kraan: Marije Koenders: declared.