C5-O-02Targeted Imaging and Theranostics with Peptides and Novel Protein Scaffolds, Repebody and Monobody

Abstract

Repebody is a binding scaffold based on variable lymphocyte receptors, which are nonimmunoglobulin antibodies composed of leucine-rich repeat modules in jawless vertebrates. Repebody can be developed against variety of epitopes by module engineering. The epidermal growth factor receptor (EGFR, HER1) autocrine pathway contributes to a number of highly relevant processes in cancer development and progression, including cell proliferation, regulation of apoptotic cell death, angiogenesis and metastatic spread. In this study, EGFR-specific repebody (RB EGFR ) and its drug conjugates were developed [ 1 ] to deliver drugs specifically into tumor cells expressing EGFR as well as to visualize the status of receptor expression and to prevent ligand binding that may inhibit autophosphorylation and downstream intracellular signaling. Monobodies are binding scaffold proteins originating from a human fibronectin domain III (Fn3) scaffold that can be easily engineered with specificity and affinity. Human EphA2 (hEphA2) is an early detection marker protein for various tumors including lung, breast, and colon cancer. In this study, we isolated two hEphA2-specific monobodies (E1 and E10) by screening a yeast surface display library [ 2 ].