Technology Listings


Reactivation of BAI1 Through Chromatin Modifiers For Tumor Suppression

Application

Vasculostatin fragments can be used as anti-angiogenic and anti-tumorigenic therapies.

Key Benefits
  • Transcription enhancement and/or post-translational cleavage of endogenous or expressed BAI1 increases the amount of vasculostatin fragments bioavailable for suppression of angiogenesis and tumorigenesis.
  • Purified vasculostatin fragments can be administered as anti-angiogenics and anti-tumorigenics.
Technical Summary

Tumorigenesis is a complex process during which transformed cells hyperproliferate to form a tumor mass. The induction of new blood vessel formation, known as angiogenesis, is an important aspect of this process, providing the tumor with access to critical nutrients. In normal tissue angiogenesis is a tightly controlled balance of numerous factors, however this process is often dysregulated in tumor cells that exhibit increased expression of pro-angiogenic factors, or decreased expression of anti-angiogenics. Therefore, factors that block angiogenesis in tumors are potential anti-cancer therapies. One such factor is the 165kDa transmembrane protein Brain Angiogenesis Inhibitor 1 (BAI1). Dr. Erwin Van Meir and colleagues at Emory University have discovered that BAI1 can be cleaved at two extracellular sites to generate soluble fragments of 120kDa (Vstat120) or 40kDa (Vstat40). Importantly, Vstat120 is found in normal brain tissue, however BAI1 is downregulated in tumors such as glioblastoma, suggesting these fragments function as tumor suppressors. These fragments contain multiple TSR binding domains and an arginine-glycine-aspartic acid (RGD) integrin binding motif which are thought to bind to endothelial cell receptors and inhibit pro-ngiogenic pathways. Vstat120 and Vstat40 can be administered through a variety of delivery mechanisms such as injection of purified or synthesized soluble protein, expression through gene or virotherapy, or even a protease capable of cleaving endogenously expressed fulllength BA1. Vstat protein therapy is therefore a viable and versatile treatment for all unregulated angiogenesis and many cancer types.

Developmental Stage & Potential Market
  • In proof-of-principle experiments Vstat120 and Vstat40 have demonstrated anti-angiogenic activity in vitro, and Vstat120 has shown anti-angiogenic and anti-tumorgenic activity rodents models.
  • Current treatments for glioblastoma include surgery, radiotherapy, and temozolomide (chemotherapy), however the mean survival after diagnosis is only 50 months.
Patent Information
App Type Country Serial No. Patent No. File Date Issued Date Expire Date
Nationalized PCT - Foreign EP 08771306.1 2155878 6/18/2008 2/24/2016 6/18/2028
Nationalized PCT - Foreign Canada 2,688,145   6/18/2008    
Continuation United States 13/892,608 6/18/2008    
Nationalized PCT - Foreign Australia 2008265840 2008265840 6/18/2008 4/30/2015 6/18/2028
Tech ID: 07054
Published: 2/24/2009
Category
Therapeutics

Contact
Justin Burns
Licensing Associate
Emory University
justin.burns@emory.edu

Inventor(s)
Erwin Van Meir

Keywords
Enzyme/Protein
Oncology