Technology ID
E-246-2012-0

Engineered Anthrax Toxin Variants that Target Cancer

Linked ID
TAB-2576
Inventors
Clinton Leysath (NIAID)
Damilola Phillips (NIAID)
Stephen Leppla (NIAID)
Lead Inventors
Clinton Leysath (NIAID)
Co-Inventors
Damilola Phillips (NIAID)
Stephen Leppla (NIAID)
Development Status
  • Pre-clinical
  • In vitro data available
  • In vivo data available (animal)
Applications
Therapeutics
Therapeutic Areas
Oncology
Immunology
ICs
NIAID
Commercial Applications
Therapeutic treatment for solid tumors, cancers, and infectious diseases.
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.
Competitive Advantages
  • 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.

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