Tumor-Suppressing Growth Factor Decoy

Tech ID: 32670 / UC Case 2017-547-0

Abstract

Researchers at the University of California, Davis have developed dominant-negative FGF2 antagonists that suppress angiogenesis and tumor growth.

Full Description

The Fibroblast growth factor-1 receptor (FGFR1) has been implicated in tumor angiogenesis and is an important target for antiangiogenic therapies. A dominant-negative FGF1 mutant (the R50E mutant) - a mutant of the FGF1 ligand that simulates the FGFR1 receptor - is currently used as an anti-cancer and anti-angiogenesis therapeutic agent. However, R50E is thermodynamically unstable - affecting its usefulness as a therapy. Therefore, there is a need for a FGF-targeting therapeutic that is just as effective as, but more stable than, R50E.

Researchers at the University of California, Davis have developed dominant-negative FGF2 mutants that are more stable than R50E. Both mutants (FGF2 decoys) have thermostability and strongly suppress angiogenesis and tumor growth. These dominant-negative FGF2 decoys bind FGFR1 and are both defective in signaling functions and to integrin binding. The decoys have been successfully tested in mouse embryonic fibroblast cells to suppress ERK1/2 activation and DNA synthesis, as well as to suppress angiogenesis in HUVEC cells (tube formation; endothelial cell migration) and sprouting in aorta ring assays.

Applications

  • Anti-angiogenic agents as tumor growth suppressor

Features/Benefits

  • Thermodynamically stable 
  • Long (7 hour) half-life in circulation 
  • Injectable Defective to integrin binding

Patent Status

Country Type Number Dated Case
United States Of America Issued Patent 11,229,681 01/25/2022 2017-547
 

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Inventors

  • Takada, Yoko K.
  • Takada, Yoshikazu

Other Information

Keywords

suppress angiogenesis, suppress tumor growth, thermodynamically stable, FGF2, FGF2 antagonist, FGF2 decoy

Categorized As