Item Details

title

TARGETING A CANCER-ASSOCIATED BIOMARKER WITH DIAGNOSTIC AND THERAPEUTIC RADIOACTIVITY

author

Nguyen, Van

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.

subject

GBM

IL13Ra2

molecular imaging

radio-immunotherapy

targeted therapy escapees

contributor

Mintz, Akiva (committee chair)

Kridel, Steven J (committee member)

Debinski, Waldemar (committee member)

High, Kevin P (committee member)

Robbins, Michael E (committee member)

date

2012-06-12T08:35:56Z (accessioned)

2014-06-12T08:30:08Z (available)

2012 (issued)

degree

Molecular Medicine and Translational Science (discipline)

embargo

2014-06-12 (terms)

identifier

http://hdl.handle.net/10339/37277 (uri)

language

en (iso)

publisher

Wake Forest University

type

Dissertation