2026-09-21T00:11:25Zhttps://wakespace.lib.wfu.edu/server/oai/request

oai:null:10339/372772026-09-02T13:09:38Zcom_10339_14934col_10339_38132

Nguyen, Van 2012-06-12T08:35:56Z 2014-06-12T08:30:08Z 2012 https://wakespace.lib.wfu.edu/handle/10339/37277 Our objective is to exploit a ligand-based delivery system for targeting diagnostic and therapeutic agents to cancers expressing IL13Ra2, a tumor-restricted plasma membrane receptor overexpressed in GBM and other malignancies. Based on prior work, we designed a novel IL13Ra2-Targeted Quadruple Mutant of IL13 (TQM13) to selectively bind the tumor-restricted IL13Ra2 with high affinity but not significantly interact with the physiologically abundant IL13Ra1/IL4Ra heterodimer expressed in normal brain. In vitro binding experiments established that TQM13 bound strongly to IL13Ra2-expressing samples but not normal brain. Importantly, unlike wtIL13, TQM13 neither functionally activates IL13Ra1/IL4Ra in cells nor binds to it in Biacore studies. Furthermore, PET imaging confirmed in vivo targeting of systemically delivered 124I-TQM13 to IL13Ra2-expressing subcutaneous GBM tumors and 131I-TQM13 demonstrated therapeutic efficacy in such animal model. Our results demonstrated that we have successfully generated optimized scaffolding with specific binding activity towards the tumor-associated IL13Ra2 in vitro and potential to deliver diagnostic and therapeutic payloads in vivo. en Wake Forest University GBM IL13Ra2 molecular imaging radio-immunotherapy targeted therapy escapees TARGETING A CANCER-ASSOCIATED BIOMARKER WITH DIAGNOSTIC AND THERAPEUTIC RADIOACTIVITY Dissertation Mintz, Akiva Kridel, Steven J Debinski, Waldemar High, Kevin P Robbins, Michael E Molecular Medicine and Translational Science 2014-06-12 restricted