| Autor: |
Cherf, Gerald M., Lee, Robert B., Mehta, Nishant, Clifford, Claire, Torres, Kathleen, Kintzing, James R., Cochran, Jennifer R. |
| Zdroj: |
Biotechnology & Bioengineering; Oct2024, Vol. 121 Issue 10, p3169-3180, 12p |
| Abstrakt: |
Urokinase‐type plasminogen activator receptor (uPAR) is overexpressed on tumor cells in multiple types of cancer and contributes to disease progression and metastasis. In this work, we engineered a novel bi‐paratopic uPAR targeting agent by fusing the binding domains of two native uPAR ligands: uPA and vitronectin, with a flexible peptide linker. The linker length was optimized to facilitate simultaneous engagement of both domains to their adjacent epitopes on uPAR, resulting in a high affinity and avid binding interaction. Furthermore, the individual domains were affinity‐matured using yeast surface display and directed evolution, resulting in a bi‐paratopic protein with affinity in the picomolar to femtomolar range. This engineered uPAR targeting agent demonstrated significantly enhanced tumor localization in mouse tumor models compared to the native uPAR ligand and warrants further investigation as a diagnostic and therapeutic agent for cancer. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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