Objectives: To investigate the efficacy of the bispecific targeted toxin, dEGFATFKDEL, on head and neck carcinoma cell lines in vitro and in vivo. Materials and Methods: A deimmunized bispecific anti-cancer agent was constructed to simultaneously target both the overexpressed EGF receptor on carcinomas and the urokinase receptor (uPAR), that is found on the endothelial cells of the neovasculature within tumors. Flow cytometry assays were performed to determine the level of EGFR expressed on a variety of carcinoma lines. These lines were then tested in tritiated leucine incorporation assays to determine the efficacy of dEGFATFKDEL. Human vein endothelial primary cells were also tested to determine the effectiveness of the ATF portion of the molecule that binds uPAR. Furthermore, mouse studies were performed to determine whether dEGFATFKDEL was effective at inhibiting tumor growth in vivo. Results: UMSCC-11B and NA, two head and neck squamous cell carcinomas, highly expressed EGFR. Both the carcinoma lines and the human vein endothelial cells were inhibited at sub-nanomolar concentrations by dEGFATFKDEL. The tumor studies showed that the tumors treated with dEGFATFKDEL were significantly inhibited whereas the negative control and untreated tumors progressed. In a separate in vivo study involving another carcinoma line, MDA-MB-231, the effectiveness of dEGFATFKDEL was confirmed. No toxicity was seen at the doses used in either of these mouse studies. Conclusions: This bispecific agent is effective in a mouse model of head and neck squamous cell carcinoma. Further study of this reagent for use in the treatment of carcinomas is warranted.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Dec 2012|
Bibliographical noteFunding Information:
This work was supported in part by the US Public Health Service Grants R01-CA36725, RO1 HL077923 awarded by the NCI and the NIAID, DHHS, the Randy Shaver Foundation, the Lion’s Children’s Cancer Fund, and the William Lawrence and Blanche Hughes Fund.
- Breast cancer
- Head and neck cancer
- Pseudomonas exotoxin
- Targeted toxins
- Xenograft model