Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican

Niklas von Spreckelsen; Colin M. Fadzen; Nina Hartrampf; Yarah Ghotmi; Justin M. Wolfe; Shipra Dubey; Bo Yeun Yang; Marie F. Kijewski; Shuyan Wang; Charlotte Farquhar; Sonja Bergmann; Mykola Zdioruk; J. Roscoe Wasserburg; Benjamin Scott; Emily Murrell; Fernanda C. Bononi; Leonard G. Luyt; Marcelo DiCarli; Martine L.M. Lamfers; Keith L. Ligon; E. Antonio Chiocca; Mariano S. Viapiano; Bradley L. Pentelute; Sean E. Lawler; Choi Fong Cho

doi:10.1002/adtp.202000244

Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican

Niklas von Spreckelsen, Colin M. Fadzen, Nina Hartrampf, Yarah Ghotmi, Justin M. Wolfe, Shipra Dubey, Bo Yeun Yang, Marie F. Kijewski, Shuyan Wang, Charlotte Farquhar, Sonja Bergmann, Mykola Zdioruk, J. Roscoe Wasserburg, Benjamin Scott, Emily Murrell, Fernanda C. Bononi, Leonard G. Luyt, Marcelo DiCarli, Martine L.M. Lamfers, Keith L. LigonE. Antonio Chiocca, Mariano S. Viapiano, Bradley L. Pentelute, Sean E. Lawler^*, Choi Fong Cho^*

^*Corresponding author for this work

Neurosurgery

Research output: Contribution to journal › Article › Academic › peer-review

15 Citations (Scopus)

Abstract

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-Bcan-Targeting Peptide (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 ¹⁸F, 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.

Original language	English
Article number	2000244
Journal	Advanced Therapeutics
Volume	4
Issue number	4
Early online date	20 Jan 2021
DOIs	https://doi.org/10.1002/adtp.202000244 https://doi.org/10.1002/adtp.202000244
Publication status	Published - Apr 2021

Bibliographical note

Acknowledgements:
N.S. is supported by the Deutsche Forschungsgemeinschaft (DFG) (research fellowship grant number 400975596). C.-F.C. is supported by the Sperling Family Foundation, Harvard Neuro-Discovery Center, BWH Women's Brain Initiative, BWH Connors Center, Brigham Research Institute and DoD (grant number W81XWH1910791). J.M.W. is supported by the National Science Foundation Graduate Research Fellowship under Grant No. 1122374. S.E.L. is supported by (NCI R01CA237063), the BWH Innovator Award, and B*CURED Foundation. B.L.P. is supported by (NCI R01CA237063). E.A.C. is supported by (RO1CA166172). L.G.L. is supported by NSERC.

Publisher Copyright: © 2021 Wiley-VCH GmbH

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von Spreckelsen, N., Fadzen, C. M., Hartrampf, N., Ghotmi, Y., Wolfe, J. M., Dubey, S., Yang, B. Y., Kijewski, M. F., Wang, S., Farquhar, C., Bergmann, S., Zdioruk, M., Wasserburg, J. R., Scott, B., Murrell, E., Bononi, F. C., Luyt, L. G., DiCarli, M., Lamfers, M. L. M., ... Cho, C. F. (2021). Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican. Advanced Therapeutics, 4(4), Article 2000244. https://doi.org/10.1002/adtp.202000244, https://doi.org/10.1002/adtp.202000244

@article{0b8af911572a45f694d74cdc5b410b96,

title = "Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican",

abstract = "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-Bcan-Targeting Peptide (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 18F, 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.",

author = "{von Spreckelsen}, Niklas and Fadzen, {Colin M.} and Nina Hartrampf and Yarah Ghotmi and Wolfe, {Justin M.} and Shipra Dubey and Yang, {Bo Yeun} and Kijewski, {Marie F.} and Shuyan Wang and Charlotte Farquhar and Sonja Bergmann and Mykola Zdioruk and Wasserburg, {J. Roscoe} and Benjamin Scott and Emily Murrell and Bononi, {Fernanda C.} and Luyt, {Leonard G.} and Marcelo DiCarli and Lamfers, {Martine L.M.} and Ligon, {Keith L.} and Chiocca, {E. Antonio} and Viapiano, {Mariano S.} and Pentelute, {Bradley L.} and Lawler, {Sean E.} and Cho, {Choi Fong}",

note = "Acknowledgements: N.S. is supported by the Deutsche Forschungsgemeinschaft (DFG) (research fellowship grant number 400975596). C.-F.C. is supported by the Sperling Family Foundation, Harvard Neuro-Discovery Center, BWH Women's Brain Initiative, BWH Connors Center, Brigham Research Institute and DoD (grant number W81XWH1910791). J.M.W. is supported by the National Science Foundation Graduate Research Fellowship under Grant No. 1122374. S.E.L. is supported by (NCI R01CA237063), the BWH Innovator Award, and B*CURED Foundation. B.L.P. is supported by (NCI R01CA237063). E.A.C. is supported by (RO1CA166172). L.G.L. is supported by NSERC. Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",

year = "2021",

month = apr,

doi = "10.1002/adtp.202000244",

language = "English",

volume = "4",

journal = "Advanced Therapeutics",

issn = "2366-3987",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "4",

}

von Spreckelsen, N, Fadzen, CM, Hartrampf, N, Ghotmi, Y, Wolfe, JM, Dubey, S, Yang, BY, Kijewski, MF, Wang, S, Farquhar, C, Bergmann, S, Zdioruk, M, Wasserburg, JR, Scott, B, Murrell, E, Bononi, FC, Luyt, LG, DiCarli, M, Lamfers, MLM, Ligon, KL, Chiocca, EA, Viapiano, MS, Pentelute, BL, Lawler, SE & Cho, CF 2021, 'Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican', Advanced Therapeutics, vol. 4, no. 4, 2000244. https://doi.org/10.1002/adtp.202000244, https://doi.org/10.1002/adtp.202000244

TY - JOUR

T1 - Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican

AU - von Spreckelsen, Niklas

AU - Fadzen, Colin M.

AU - Hartrampf, Nina

AU - Ghotmi, Yarah

AU - Wolfe, Justin M.

AU - Dubey, Shipra

AU - Yang, Bo Yeun

AU - Kijewski, Marie F.

AU - Wang, Shuyan

AU - Farquhar, Charlotte

AU - Bergmann, Sonja

AU - Zdioruk, Mykola

AU - Wasserburg, J. Roscoe

AU - Scott, Benjamin

AU - Murrell, Emily

AU - Bononi, Fernanda C.

AU - Luyt, Leonard G.

AU - DiCarli, Marcelo

AU - Lamfers, Martine L.M.

AU - Ligon, Keith L.

AU - Chiocca, E. Antonio

AU - Viapiano, Mariano S.

AU - Pentelute, Bradley L.

AU - Lawler, Sean E.

AU - Cho, Choi Fong

N1 - Acknowledgements: N.S. is supported by the Deutsche Forschungsgemeinschaft (DFG) (research fellowship grant number 400975596). C.-F.C. is supported by the Sperling Family Foundation, Harvard Neuro-Discovery Center, BWH Women's Brain Initiative, BWH Connors Center, Brigham Research Institute and DoD (grant number W81XWH1910791). J.M.W. is supported by the National Science Foundation Graduate Research Fellowship under Grant No. 1122374. S.E.L. is supported by (NCI R01CA237063), the BWH Innovator Award, and B*CURED Foundation. B.L.P. is supported by (NCI R01CA237063). E.A.C. is supported by (RO1CA166172). L.G.L. is supported by NSERC. Publisher Copyright: © 2021 Wiley-VCH GmbH

PY - 2021/4

Y1 - 2021/4

N2 - 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-Bcan-Targeting Peptide (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 18F, 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.

AB - 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-Bcan-Targeting Peptide (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 18F, 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.

UR - http://www.scopus.com/inward/record.url?scp=85104211803&partnerID=8YFLogxK

U2 - 10.1002/adtp.202000244

DO - 10.1002/adtp.202000244

M3 - Article

C2 - 33997269

AN - SCOPUS:85104211803

SN - 2366-3987

VL - 4

JO - Advanced Therapeutics

JF - Advanced Therapeutics

IS - 4

M1 - 2000244

ER -

Targeting Glioblastoma Using a Novel Peptide Specific to a Deglycosylated Isoform of Brevican

Abstract

Bibliographical note

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