TY  - JOUR
AU  - Smeets, Esther M. M.
AU  - Dorst, Daphne N.
AU  - Franssen, Gerben M.
AU  - van Essen, Merijn S.
AU  - Frielink, Cathelijne
AU  - Stommel, Martijn W. J.
AU  - Trajkovic-Arsic, Marija
AU  - Cheung, Phyllis F.
AU  - Siveke, Jens
AU  - Wilson, Ian
AU  - Mascioni, Alessandro
AU  - Aarntzen, Erik H. J. G.
AU  - van Lith, Sanne A. M.
TI  - Fibroblast Activation Protein-Targeting Minibody-IRDye700DX for Ablation of the Cancer-Associated Fibroblast with Photodynamic Therapy
JO  - Cells
VL  - 12
IS  - 10
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DKFZ-2023-01129
SP  - 1420
PY  - 2023
AB  - Fibroblast activation protein (FAP), expressed on cancer-associated fibroblasts, is a target for diagnosis and therapy in multiple tumour types. Strategies to systemically deplete FAP-expressing cells show efficacy; however, these induce toxicities, as FAP-expressing cells are found in normal tissues. FAP-targeted photodynamic therapy offers a solution, as it acts only locally and upon activation. Here, a FAP-binding minibody was conjugated to the chelator diethylenetriaminepentaacetic acid (DTPA) and the photosensitizer IRDye700DX (DTPA-700DX-MB). DTPA-700DX-MB showed efficient binding to FAP-overexpressing 3T3 murine fibroblasts (3T3-FAP) and induced the protein’s dose-dependent cytotoxicity upon light exposure. Biodistribution of DTPA-700DX-MB in mice carrying either subcutaneous or orthotopic tumours of murine pancreatic ductal adenocarcinoma cells (PDAC299) showed maximal tumour uptake of 111In-labelled DTPA-700DX-MB at 24 h post injection. Co-injection with an excess DTPA-700DX-MB reduced uptake, and autoradiography correlated with FAP expression in the stromal tumour region. Finally, in vivo therapeutic efficacy was determined in two simultaneous subcutaneous PDAC299 tumours; only one was treated with 690 nm light. Upregulation of an apoptosis marker was only observed in the treated tumours. In conclusion, DTPA-700DX-MB binds to FAP-expressing cells and targets PDAC299 tumours in mice with good signal-to-background ratios. Furthermore, the induced apoptosis indicates the feasibility of targeted depletion of FAP-expressing cells with photodynamic therapy.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.3390/cells12101420
UR  - https://inrepo02.dkfz.de/record/276748
ER  -