Preclinical validation of a novel metastasis-inhibiting Tie1 function-blocking antibody

EMBO Mol Med. 2020 Jun 8;12(6):e11164. doi: 10.15252/emmm.201911164. Epub 2020 Apr 17.


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.

Keywords: angiogenesis; angiopoietin-Tie signaling; cancer; endothelial cells; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-1
  • Angiopoietin-2
  • Animals
  • Gene Deletion
  • Humans
  • Mice
  • Neoplasms*
  • Neovascularization, Pathologic
  • Receptor, TIE-1* / genetics
  • Receptor, TIE-2


  • Angiopoietin-1
  • Angiopoietin-2
  • Receptor, TIE-1
  • Receptor, TIE-2

Associated data

  • GEO/GSE144851