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

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title
LOCO-REGIONALLY TARGETING INTERLEUKIN-13 RECEPTOR ALPHA-2 AND MAXIMIZING THERAPEUTIC ACCESS TO GLIOBLASTOMAS USING BIOMARKER DIRECTED ALPHA PARTICLES
author
Sattiraju, Anirudh
abstract
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.
subject
Alpha particles
Blood brain barrier
Drug delivery
Glioblastoma
IL13RA2
Integrin alpha-v beta-3
contributor
Mintz, Akiva (committee chair)
Debinski, Waldemar (committee member)
Dorsey, Jay (committee member)
Kridel, Steve (committee member)
Sai, Kiran Kumar Solingapuram (committee member)
date
2018-08-23T08:35:38Z (accessioned)
2020-08-22T08:30:17Z (available)
2018 (issued)
degree
Cancer Biology (discipline)
embargo
2020-08-22 (terms)
identifier
http://hdl.handle.net/10339/92381 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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