LOCO-REGIONALLY TARGETING INTERLEUKIN-13 RECEPTOR ALPHA-2 AND MAXIMIZING THERAPEUTIC ACCESS TO GLIOBLASTOMAS USING BIOMARKER DIRECTED ALPHA PARTICLES

Currently approved conventional therapies for glioblastoma (GBM) patients have only increased their overall survival by about 20.8 months without providing a substantial benefit to their quality of life. Personalized medicine by targeting biomarkers that are overexpressed specifically by patients’ GBMs are proving to be a sophisticated strategy for loco-regionally delivering therapies. Interleukin-13 receptor alpha-2 (IL13RA2) is one such GBM restricted biomarker which was previously discovered to be highly upregulated in about 75% of GBM samples and found to be an effective target for delivering tumor-specific cytotoxic therapeutics (Debinski et al, Clinical Cancer Research 1999; Mintz et al, Neoplasia 2002). IL13RA2 was also shown to be overexpressed by therapy resistant, diving GBM stem-like cells (GSCs) (Nguyen et al, Translational Oncology 2011). Targeting such a GBM restricted biomarker, especially one that is also expressed by GSCs to deliver cytotoxic therapeutics and diagnostic agents could potentially lead to early diagnosis and result in an increase in patient survival. A linearized heptapeptide, Pep-1L was previously reported to bind specifically to IL13RA2 through in vitro, in vivo and ex vivo analyses (Pandya et al, Neurooncology 2012). Peptides are advantageous compared to using larger proteins and antibodies to deliver therapies to tumors due to their small size which results in relatively brisk plasma clearance. My dissertation includes and summarizes reports where we evaluated the feasibility of delivering a loco-regional cy to IL13RA2 expressing GBMs using Pep-1L and where we addressed potential challenges due to ineffective therapeutic delivery and disease recurrence.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2018

Author dc:creator

• Sattiraju, Anirudh

• Alpha particles

Language dc:language.iso

en

Handle dc:identifier.uri

http://hdl.handle.net/10339/92381

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/92381