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@ARTICLE{Dorst:277783,
      author       = {D. N. Dorst and E. M. M. Smeets and C. Klein and C.
                      Frielink and D. Geijs and M. Trajkovic-Arsic$^*$ and P. F.
                      Y. Cheung$^*$ and M. W. J. Stommel and M. Gotthardt and J.
                      T. Siveke$^*$ and E. H. J. G. Aarntzen and S. A. M. van
                      Lith},
      title        = {{F}ibroblast {A}ctivation {P}rotein-{T}argeted
                      {P}hotodynamic {T}herapy of {C}ancer-{A}ssociated
                      {F}ibroblasts in {M}urine {M}odels for {P}ancreatic {D}uctal
                      {A}denocarcinoma.},
      journal      = {Molecular pharmaceutics},
      volume       = {20},
      number       = {8},
      issn         = {1543-8384},
      address      = {Washington, DC},
      publisher    = {American Chemical Society},
      reportid     = {DKFZ-2023-01498},
      pages        = {4319-4330},
      year         = {2023},
      note         = {2023 Aug 7;20(8):4319-4330},
      abstract     = {Patients with pancreatic ductal adenocarcinoma (PDAC) have
                      a dismal 5 year survival of $9\%.$ One important limiting
                      factor for treatment efficacy is the dense tumor-supporting
                      stroma. The cancer-associated fibroblasts in this stroma
                      deposit excessive amounts of extracellular matrix components
                      and anti-inflammatory mediators, which hampers the efficacy
                      of chemo- and immunotherapies. Systemic depletion of all
                      activated fibroblasts is, however, not feasible nor
                      desirable and therefore a local approach should be pursued.
                      Here, we provide a proof-of-principle of using fibroblast
                      activation protein (FAP)-targeted photodynamic therapy
                      (tPDT) to treat PDAC. FAP-targeting antibody 28H1 and
                      irrelevant control antibody DP47GS were conjugated to the
                      photosensitizer IRDye700DX (700DX) and the chelator
                      diethylenetriaminepentaacetic acid. In vitro binding and
                      cytotoxicity were evaluated using the fibroblast cell-line
                      NIH-3T3 stably transfected with FAP. Biodistribution of
                      111In-labeled antibody-700DX constructs was determined in
                      mice carrying syngeneic tumors of the murine PDAC cell line
                      PDAC299, and in a genetically engineered PDAC mouse model
                      (CKP). Then, tPDT was performed by exposing the subcutaneous
                      or the spontaneous PDAC tumors to 690 nm light. Induction of
                      apoptosis after treatment was assessed using automated
                      analyses of immunohistochemistry for cleaved caspase-3.
                      28H1-700DX effectively bound to 3T3-FAP cells and induced
                      cytotoxicity upon exposure to 690 nm light, whereas no
                      binding or cytotoxic effects were observed for DP47GS-700DX.
                      Although both 28H1-700DX and DP47GS-700DX accumulated in
                      subcutaneous PDAC299 tumors, autoradiography demonstrated
                      that only 28H1-700DX reached the tumor core. On the
                      contrary, control antibody DP47GS-700DX was only present at
                      the tumor rim. In CKP mice, both antibodies accumulated in
                      the tumor, but tumor-to-blood ratios of 28H1-700DX were
                      higher than that of the control. Notably, in vivo FAP-tPDT
                      caused upregulation of cleaved caspase-3 staining in both
                      subcutaneous and in spontaneous tumors. In conclusion, we
                      have shown that tPDT is a feasible approach for local
                      depletion of FAP-expressing stromal cells in murine models
                      for PDAC.},
      keywords     = {cancer-associated fibroblast (CAF) (Other) / fibroblast
                      activation protein (FAP) (Other) / pancreatic ductal
                      adenocarcinoma (PDAC) (Other) / syngeneic models (Other) /
                      targeted photodynamic therapy (tPDT) (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37485886},
      doi          = {10.1021/acs.molpharmaceut.3c00453},
      url          = {https://inrepo02.dkfz.de/record/277783},
}