Targeting EGFR and uPAR on human rhabdomyosarcoma, osteosarcoma, and ovarian adenocarcinoma with a bispecific ligand-directed toxin

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Purpose: Human sarcomas are rare and difficult to treat cancerous tumors typically arising from soft tissue or bone. Conversely, carcinomas are the most common cancer subtype in humans and the primary cause of mortality across all cancer patients. While conventional therapeutic modalities can prolong disease-free intervals and survival in some cases, treatment of refractory or recurrent solid tumors is challenging, and tumor-related mortality remains unacceptably high. The identification of overexpressed cell surface receptors on sarcoma and carcinoma cells has provided a valuable tool to develop targeted toxins as an alternative anticancer strategy. Recent investigation of recombinant protein-linked toxins that specifically target these cancer receptors has led to the development of highly specific, cytotoxic, and deimmunized drugs that can kill cancer cells. Methods: This study investigated a recombinant protein called epidermal growth factor bispecific angiotoxin (eBAT), which is designed to target the epidermal growth factor receptor (EGFR) on cancer cells and the urokinase plasminogen activator receptor (uPAR) on cancer cells and associated tumor vasculature. Both receptors are expressed by a variety of human sarcomas and carcinomas. Flow cytometry techniques were used to determine binding affinity of eBAT to cancer cells, and proliferation assays were performed to calculate tumor killing ability based on half-maximal inhibitory concentrations. Results: eBAT demonstrated cytotoxicity against a variety of sarcoma and carcinoma cells that overexpress EGFR and uPAR in vitro and showed greater cell killing ability and binding affinity to cancer cells compared with its monospecific counterparts. Conclusion: The results of our study are promising, and further studies will be necessary to confirm the applicability of eBAT as a supplementary therapy for a variety of sarcomas, carcinomas, and possibly other refractory malignancies that express EGFR and uPAR.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalClinical Pharmacology: Advances and Applications
StatePublished - 2018

Bibliographical note

Funding Information:
This work was supported in part by the US Public Health Service Grant R01-CA36725, R01-CA72669, P01-CA65493, P01-CA111412, and R35 CA197292 awarded by the NCI and the NIAID, DHHS. It was also supported by an NIH Research Evaluation and Commercialization Hub (REACH) Award (U01), the Killebrew-Thompson Memorial Golf Tournament, the Lion Fund, William Lawrence and Blanche Hughes Fund, the Randy Shaver Research and Community Foundation, the Atwater Cancer Drug Development Award, the Deutsche Krebshilfe (J.U.S., 111548), and a CETI translational award from the University of Minnesota Masonic Cancer Center.

Publisher Copyright:
© 2018 Oh et al.


  • Carcinoma
  • EGFR
  • Sarcoma
  • eBAT
  • uPAR


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