Engineered Anthrax Toxin Variants that Target Cancer


This technology describes the use of novel mutated anthrax protective antigen (PA) protein variants to target tumor cells and tumor vasculature. NIH scientists have engineered two PA variants that selectively complement one another and combine to form active octamers that target tumor cells. This controlled oligomeric activation of the PA proteins makes the likelihood of toxicity to non-tumor cells very low since non-tumor tissue does not express certain cell-surface proteases required to activate the PA variants. Using proteases that are highly expressed in tumor cells, e.g., matrix metalloproteases (MMP) and urokinase plasminogen activator (uPA), the scientists have shown significant tumor growth suppression with the oligomer in a mouse model. Furthermore, other tumor-specific proteases could also be used to control formation of the targeted octameric anthrax toxin structures. Moreover, the structures can be expanded to include several PA variants. In summary, this technology provides a unique, expandable platform that reduces toxicity to normal tissues compared to other systems and can be used to treat cancers more effectively.

Potential Commercial Applications: Competitive Advantages:
Therapeutic treatment for solid tumors, cancers, and infectious diseases. 
  • Specificity in targeting tumors while eliminating side effects associated with non-specific targeting of normal cells
  • Method can be expanded to include different proteases and up to eight PA variants.


Development Stage:
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)


Related Invention(s):




Inventors:

Stephen Leppla (NIDCR)  ➽ more inventions...

Clinton Leysath (NIAID)  ➽ more inventions...

Damilola Phillips (NIAID)  ➽ more inventions...


Intellectual Property:
US Application No. 61/692,143
PCT Application No. PCT/US2013/056205
US Application No. 14/423,408

Publications:
Phillips DD, et al. PMID 23393143

Collaboration Opportunity:

The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this invention. For collaboration opportunities, please contact Dr. Natalie Greco at Natalie.Greco@nih.gov or 301-761-7898.


Licensing Contact:
Wade Green,
Email: wade.green@nih.gov
Phone: 301-761-7505

OTT Reference No: E-246-2012/0
Updated: Jul 6, 2017