Presentation Abstract

Abstract Number: 582
Presentation Title: Targeting the blood-brain barrier with a non-canonical iron-mimicry mechanism: A translational approach for the detection and treatment of human brain tumors
Presentation Time: Sunday, Apr 18, 2010, 2:00 PM - 5:00 PM
Location: Exhibit Hall A-C, Poster Section 22
Poster Section: 22
Poster Board Number: 3
Author Block: Fernanda I. Staquicini1, Michael G. Ozawa1, Catherine A. Moya1, Wouter H.P. Driessen1, Elena Magda Barbu1, Suren Soghomonyan1, Leo G. Flores 2nd1, Mian M. Alauddin1, Juri G. Gelovani1, Xiaowen Liang2, Magnus Hook3, James P. Basilion4, Oliver Bogler1, Richard L. Sidman5, Webster K. Cavenee6, Renata Pasqualini1, Wadih Arap1. 1University of Texas M. D. Anderson Cancer Center, Houston, TX; 2Texas A&M University system Health Science Center, Houston, TX; 3Texas A&M University System Health Science Center, Houston, TX; 4Case Western Reserve University, Cleveland, OH; 5Harvad Medical School, Boston, MA; 6University of California San Diego, San Diego, CA
Abstract Body: Treatment of central nervous system (CNS) diseases is limited by the blood-brain barrier (BBB), a selective vascular interface restricting passage of most molecules from blood into brain. Here we used the in vivo phage display technology to isolate peptide-targeted phage particles that can cross the BBB under normal and pathological conditions. We show that a non-canonical association of (i) transferrin, (ii) an iron-mimic ligand motif, and (iii) transferrin receptor mediates binding and transport of phage particles into the normal mouse brain through an allosteric mechanism. We also show that, in an orthotopic human glioma model, a combination of transferrin receptor overexpression plus extended vascular permeability and ligand retention results in remarkable brain tumor targeting. Such unique attributes enable molecular imaging and targeted therapy of intracranial tumors in a clinic-ready setting. Finally, we expand our data by analyzing a large panel of primary CNS tumors through comprehensive tissue microarrays. Together, our approach and results provide a translational avenue for the detection and treatment of brain tumors.