Immunotoxin chimeras of DNaseI and cytolethal distending toxin (CdtB subunit) are an effective therapeutic against epithelial tumors.
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.
- Produce less side effects than current immunotherapeutics
- Specific to highly proliferative cells
- Effectively targets head and neck cancers
Dr. Joseph M. DiRienzo
State of Development:
In vitro proof of concept
US 8,920,809 B2 “Chimera comprising bacterial cytotoxin and methods of using the same” (issued Dec. 30, 2014)
- Sponsored research
- Research Collaboration
Docket # S4288