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@ARTICLE{Singhal:154523,
      author       = {M. Singhal$^*$ and N. Gengenbacher$^*$ and S. La Porta$^*$
                      and S. Gehrs$^*$ and J. Shi$^*$ and M. Kamiyama$^*$ and D.
                      M. Bodenmiller and A. Fischl and B. Schieb$^*$ and E.
                      Besemfelder$^*$ and S. Chintharlapalli and H. Augustin$^*$},
      title        = {{P}reclinical validation of a novel metastasis-inhibiting
                      {T}ie1 function-blocking antibody.},
      journal      = {EMBO molecular medicine},
      volume       = {12},
      number       = {6},
      issn         = {1757-4684},
      address      = {Heidelberg},
      publisher    = {EMBO Press},
      reportid     = {DKFZ-2020-00844},
      pages        = {e11164},
      year         = {2020},
      note         = {DKFZ-ZMBH Alliance2020 Jun 8;12(6):e11164#EA:A190#LA:A190#},
      abstract     = {The angiopoietin (Ang)-Tie pathway has been intensely
                      pursued as candidate second-generation anti-angiogenic
                      target. While much of the translational work has focused on
                      the ligand Ang2, the clinical efficacy of Ang2-targeting
                      drugs is limited and failed to improve patient survival. In
                      turn, the orphan receptor Tie1 remains therapeutically
                      unexplored, although its endothelial-specific genetic
                      deletion has previously been shown to result in a strong
                      reduction in metastatic growth. Here, we report a novel Tie1
                      function-blocking antibody (AB-Tie1-39), which suppressed
                      postnatal retinal angiogenesis. During primary tumor growth,
                      neoadjuvant administration of AB-Tie1-39 strongly impeded
                      systemic metastasis. Furthermore, the administration of
                      AB-Tie1-39 in a perioperative therapeutic window led to a
                      significant survival advantage as compared to
                      control-IgG-treated mice. Additional in vivo experimental
                      metastasis and in vitro transmigration assays concurrently
                      revealed that AB-Tie1-39 treatment suppressed tumor cell
                      extravasation at secondary sites. Taken together, the data
                      phenocopy previous genetic work in endothelial Tie1 KO mice
                      and thereby validate AB-Tie1-39 as a Tie1 function-blocking
                      antibody. The study establishes Tie1 as a therapeutic target
                      for metastasis in a perioperative or neoadjuvant setting.},
      cin          = {A190 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)A190-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {311 - Signalling pathways, cell and tumor biology
                      (POF3-311)},
      pid          = {G:(DE-HGF)POF3-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:32302470},
      doi          = {10.15252/emmm.201911164},
      url          = {https://inrepo02.dkfz.de/record/154523},
}