{"id":{"repo_id":"wfu","oai_identifier":"oai:wakespace.lib.wfu.edu:10339/37277"},"canonical_url":"https://search.dev.ndltd.org/etd/wfu/oai:wakespace.lib.wfu.edu:10339/37277","repository":{"repo_id":"wfu","name":"Wake Forest University","base_url":"https://wakespace.lib.wfu.edu/oai/request"},"display":{"title":"TARGETING A CANCER-ASSOCIATED BIOMARKER WITH DIAGNOSTIC AND THERAPEUTIC RADIOACTIVITY","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Nguyen, Van"],"institution":"Wake Forest University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012","date_published":"2012","updated_at":"2026-07-27T22:01:27Z","subjects":["GBM"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10339/37277","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Nguyen, Van"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2012-06-12T08:35:56Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2014-06-12T08:30:08Z"]},{"key":"dc:date.issued","label":"Date","values":["2012"]},{"key":"dc:publisher","label":"Institution","values":["Wake Forest University"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["GBM"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10339/37277"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:title","label":"Title","values":["TARGETING A CANCER-ASSOCIATED BIOMARKER WITH DIAGNOSTIC AND THERAPEUTIC RADIOACTIVITY"]}]}],"canonical_facts":{"dc:creator":["Nguyen, Van"],"dc:date.accessioned":["2012-06-12T08:35:56Z"],"dc:date.available":["2014-06-12T08:30:08Z"],"dc:date.issued":["2012"],"dc:description.abstract":["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."],"dc:identifier.uri":["http://hdl.handle.net/10339/37277"],"dc:language.iso":["en"],"dc:publisher":["Wake Forest University"],"dc:subject":["GBM"],"dc:title":["TARGETING A CANCER-ASSOCIATED BIOMARKER WITH DIAGNOSTIC AND THERAPEUTIC RADIOACTIVITY"],"dc:type":["Dissertation"]},"updated_at":"2026-07-27T22:01:27Z"}