Ligand-targeted toxins (LTTs) are bioengineered molecules which are composed of a targeting component linked to a toxin that induces cell death once the LTT binds its target. Bispecific targeting allows for the simultaneous targeting of two receptors. In this review, we mostly focus on the epidermal growth factor receptor (EGFR) as a target. We discuss the development and testing of a bispecific LTT targeting EGFR and urokinase-type plasminogen activator receptor (uPAR) as two attractive targets implicated in tumor growth and in the regulation of the tumor microvasculature in solid tumors. In vitro and mouse xenograft studies have shown that EGFR-targeted bispecific angiotoxin (eBAT) is effective against human solid tumors. Canine studies have shown that eBAT is both safe and effective against canine hemangiosarcoma, which is physiologically similar to human angiosarcoma. Finding the appropriate dosing strategy and sequencing of eBAT administration, in combination with other therapeutics, are among important factors for future directions. Together, the data indicate that eBAT targets cancer stem cells, it may have a role in inhibiting human tumor vasculature, and its bispecific conformation may have a role in reducing toxicity in comparative oncologic trials in dogs.
Bibliographical noteFunding Information:
Funding: J.F.M. is supported by the Alvin and June Perlman Endowed Chair in Animal Oncology. D.A.V. is supported by the Lion’s Research Fund. Funding for the work with eBAT was sourced from the Sarcoma Foundation of America, the University of Minnesota Sarcoma Translational Working Group, the Randy Shaver Cancer Research and Community Foundation, and a CETI Translational Award from the University of Minnesota Masonic Cancer Center.
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
- EGFR (epidermal growth factor receptor)
- LTT (ligand-targeted toxin)
- uPAR (urokinase-type plasminogen activator receptor)