Targeted photodynamic therapy selectively kills activated fibroblasts in experimental arthritis.

Autor:	Dorst DN; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., Rijpkema M; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Boss M; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Walgreen B; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., Helsen MMA; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., Bos DL; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Brom M; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Klein C; Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich, Schlieren, Switzerland., Laverman P; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., van der Kraan PM; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., Gotthardt M; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Koenders MI; Department of Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands., Buitinga M; Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2020 Dec 01; Vol. 59 (12), pp. 3952-3960.
DOI:	10.1093/rheumatology/keaa295
Abstrakt:	Objective: In RA, synovial fibroblasts become activated. These cells express fibroblast activation protein (FAP) and contribute to the pathogenesis by producing cytokines, chemokines and proteases. Selective depletion in inflamed joints could therefore constitute a viable treatment option. To this end, we developed and tested a new therapeutic strategy based on the selective destruction of FAP-positive cells by targeted photodynamic therapy (tPDT) using the anti-FAP antibody 28H1 coupled to the photosensitizer IRDye700DX. Methods: After conjugation of IRDye700DX to 28H1, the immunoreactive binding and specificity of the conjugate were determined. Subsequently, tPDT efficiency was established in vitro using a 3T3 cell line stably transfected with FAP. The biodistribution of [111In]In-DTPA-28H1 with and without IRDye700DX was assessed in healthy C57BL/6N mice and in C57BL/6N mice with antigen-induced arthritis. The potential of FAP-tPDT to induce targeted damage was determined ex vivo by treating knee joints from C57BL/6N mice with antigen-induced arthritis 24 h after injection of the conjugate. Finally, the effect of FAP-tPDT on arthritis development was determined in mice with collagen-induced arthritis. Results: 28H1-700DX was able to efficiently induce FAP-specific cell death in vitro. Accumulation of the anti-FAP antibody in arthritic knee joints was not affected by conjugation with the photosensitizer. Arthritis development was moderately delayed in mice with collagen-induced arthritis after FAP-tPDT. Conclusion: Here we demonstrate the feasibility of tPDT to selectively target and kill FAP-positive fibroblasts in vitro and modulate arthritis in vivo using a mouse model of RA. This approach may have therapeutic potential in (refractory) arthritis. (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
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