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Immunotoxin Therapeutic Targets Epithelial Derived Cancers

Description:

Immunotoxin chimeras of DNaseI and cytolethal distending toxin (CdtB subunit) are an effective therapeutic against epithelial tumors. 

 

Technology Overview: 

Immortalized epithelioid cell lines are sensitive to CdtB, whereas cells of mesenchymal, or ectomesenchymal origin are relatively resistant. Unique chimeras of the cdtB gene and human type I deoxyribonuclease (DNase I) were constructed to increase activity resulting in the inhibition of proliferation of human epithelial cells.  These CdtB/DNase I hybrid proteins exhibited in vitro DNA nicking/cutting activity and formed heterotrimers with CdtA and CdtC subunits to create a biologically active toxin that is active in vivo.

 

Replacement of the CdtA subunit with an anti-CD133 monoclonal antibody resulted in the targeted inhibition of CD133-expressing head and neck squamous cell carcinoma cell lines. The use of human DNase I adds a human protein signature to the CdtB toxin enhancing its application as an attractive anti-cancer cell therapy.   

 

 

Advantages: 

  • Produce less side effects than current immunotherapeutics
  • Specific to highly proliferative cells
  • Effectively targets head and neck cancers

Inventor:

Dr. Joseph M. DiRienzo 

 

State of Development: 

In vitro proof of concept 

 

Intellectual Property: 

US 8,920,809 B2 “Chimera comprising bacterial cytotoxin and methods of using the same” (issued Dec. 30, 2014)

 

Desired Partnerships: 

  • License
  • Sponsored research
  • Research Collaboration

Docket # S4288

 

Download PDF

 


Patent Information:
For Information, Contact:
Melissa Kelly
Associate Director
University of Pennsylvania
215-898-9877
kellymel@upenn.edu
Inventors:
Joseph Dirienzo
Keywords:
Immunotherapy
Oncology