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Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican
Author(s) -
Spreckelsen Niklas,
Fadzen Colin M.,
Hartrampf Nina,
Ghotmi Yarah,
Wolfe Justin M.,
Dubey Shipra,
Yang Bo Yeun,
Kijewski Marie F.,
Wang Shuyan,
Farquhar Charlotte,
Bergmann Sonja,
Zdioruk Mykola,
Wasserburg J. Roscoe,
Scott Benjamin,
Murrell Emily,
Boi Fernanda C.,
Luyt Leonard G.,
DiCarli Marcelo,
Lamfers Martine L. M.,
Ligon Keith L.,
Chiocca E. Antonio,
Viapiano Mariano S.,
Pentelute Bradley L.,
Lawler Sean E.,
Cho ChoiFong
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202000244
Subject(s) - gene isoform , peptide , glioma , cancer research , downregulation and upregulation , glioblastoma , chemistry , biology , microbiology and biotechnology , biochemistry , gene
Glioblastoma (GBM) is the most common and deadliest form of brain tumor and remains amongst the most difficult cancers to treat. Brevican (Bcan), a central nervous system (CNS)‐specific extracellular matrix protein, is upregulated in high‐grade glioma cells, including GBM. A Bcan isoform lacking most glycosylation, dg‐Bcan, is found only in GBM tissues. Here, dg‐Bcan is explored as a molecular target for GBM. In this study, a d ‐peptide library is screened to identify a small 8‐amino acid dg‐ B can‐ T argeting P eptide (BTP) candidate, called BTP‐7 that binds dg‐Bcan with high affinity and specificity. BTP‐7 is preferentially internalized by dg‐Bcan‐expressing patient‐derived GBM cells. To demonstrate GBM targeting, BTP‐7 is radiolabeled with 18 F, a radioisotope of fluorine, and increased radiotracer accumulation is found in intracranial GBM established in mice using positron emission tomography (PET) imaging. dg‐Bcan is an attractive molecular target for GBM, and BTP‐7 represents a promising lead candidate for further development into novel imaging agents and targeted therapeutics.