Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma

Mahua Dey; Dou Yu; Deepak Kanojia; Gina Li; Madina Sukhanova; Drew A. Spencer; Katatzyna C. Pituch; Lingjiao Zhang; Yu Han; Atique Uddin Ahmed; Karen S. Aboody; Maciej S Lesniak; Irina V Balyasnikova

doi:10.1016/j.stemcr.2016.07.024

Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma

Mahua Dey, Dou Yu, Deepak Kanojia, Gina Li, Madina Sukhanova, Drew A. Spencer, Katatzyna C. Pituch, Lingjiao Zhang, Yu Han, Atique Uddin Ahmed, Karen S. Aboody, Maciej S Lesniak, Irina V Balyasnikova^*

^*Corresponding author for this work

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

44 Scopus citations

Abstract

The challenges to effective drug delivery to brain tumors are twofold: (1) there is a lack of non-invasive methods of local delivery and (2) the blood-brain barrier limits systemic delivery. Intranasal delivery of therapeutics to the brain overcomes both challenges. In mouse model of malignant glioma, we observed that a small fraction of intranasally delivered neural stem cells (NSCs) can migrate to the brain tumor site. Here, we demonstrate that hypoxic preconditioning or overexpression of CXCR4 significantly enhances the tumor-targeting ability of NSCs, but without altering their phenotype only in genetically modified NSCs. Modified NSCs deliver oncolytic virus to glioma more efficiently and extend survival of experimental animals in the context of radiotherapy. Our findings indicate that intranasal delivery of stem cell-based therapeutics could be optimized for future clinical applications, and allow for safe and repeated administration of biological therapies to brain tumors and other CNS disorders.

Original language	English (US)
Pages (from-to)	471-482
Number of pages	12
Journal	Stem cell reports
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.stemcr.2016.07.024
State	Published - Sep 13 2016

Funding

This work was supported by NIH R01NS087990 (M.S.L., I.V.B.) and U01NS069997 (M.S.L.), and NIH/NRCDP K-12 award (M.D.). We thank Dr. Meijing Wu for her contributions to data analysis. We are grateful to Dr. C. David James for providing patient-derived GBM6 and GBM43 cell lines. K.S.A. is an uncompensated Board Member, Chief Scientific Officer, and shareholder of TheraBiologics.

ASJC Scopus subject areas

Genetics
Biochemistry
Cell Biology
Developmental Biology

Access to Document

10.1016/j.stemcr.2016.07.024

Cite this

@article{f6a3557d051340fba79cdf9e6ecdeec6,

title = "Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma",

abstract = "The challenges to effective drug delivery to brain tumors are twofold: (1) there is a lack of non-invasive methods of local delivery and (2) the blood-brain barrier limits systemic delivery. Intranasal delivery of therapeutics to the brain overcomes both challenges. In mouse model of malignant glioma, we observed that a small fraction of intranasally delivered neural stem cells (NSCs) can migrate to the brain tumor site. Here, we demonstrate that hypoxic preconditioning or overexpression of CXCR4 significantly enhances the tumor-targeting ability of NSCs, but without altering their phenotype only in genetically modified NSCs. Modified NSCs deliver oncolytic virus to glioma more efficiently and extend survival of experimental animals in the context of radiotherapy. Our findings indicate that intranasal delivery of stem cell-based therapeutics could be optimized for future clinical applications, and allow for safe and repeated administration of biological therapies to brain tumors and other CNS disorders.",

author = "Mahua Dey and Dou Yu and Deepak Kanojia and Gina Li and Madina Sukhanova and Spencer, {Drew A.} and Pituch, {Katatzyna C.} and Lingjiao Zhang and Yu Han and Ahmed, {Atique Uddin} and Aboody, {Karen S.} and Lesniak, {Maciej S} and Balyasnikova, {Irina V}",

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s)",

year = "2016",

month = sep,

day = "13",

doi = "10.1016/j.stemcr.2016.07.024",

language = "English (US)",

volume = "7",

pages = "471--482",

journal = "Stem cell reports",

issn = "2213-6711",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma

AU - Dey, Mahua

AU - Yu, Dou

AU - Kanojia, Deepak

AU - Li, Gina

AU - Sukhanova, Madina

AU - Spencer, Drew A.

AU - Pituch, Katatzyna C.

AU - Zhang, Lingjiao

AU - Han, Yu

AU - Ahmed, Atique Uddin

AU - Aboody, Karen S.

AU - Lesniak, Maciej S

AU - Balyasnikova, Irina V

PY - 2016/9/13

Y1 - 2016/9/13

N2 - The challenges to effective drug delivery to brain tumors are twofold: (1) there is a lack of non-invasive methods of local delivery and (2) the blood-brain barrier limits systemic delivery. Intranasal delivery of therapeutics to the brain overcomes both challenges. In mouse model of malignant glioma, we observed that a small fraction of intranasally delivered neural stem cells (NSCs) can migrate to the brain tumor site. Here, we demonstrate that hypoxic preconditioning or overexpression of CXCR4 significantly enhances the tumor-targeting ability of NSCs, but without altering their phenotype only in genetically modified NSCs. Modified NSCs deliver oncolytic virus to glioma more efficiently and extend survival of experimental animals in the context of radiotherapy. Our findings indicate that intranasal delivery of stem cell-based therapeutics could be optimized for future clinical applications, and allow for safe and repeated administration of biological therapies to brain tumors and other CNS disorders.

AB - The challenges to effective drug delivery to brain tumors are twofold: (1) there is a lack of non-invasive methods of local delivery and (2) the blood-brain barrier limits systemic delivery. Intranasal delivery of therapeutics to the brain overcomes both challenges. In mouse model of malignant glioma, we observed that a small fraction of intranasally delivered neural stem cells (NSCs) can migrate to the brain tumor site. Here, we demonstrate that hypoxic preconditioning or overexpression of CXCR4 significantly enhances the tumor-targeting ability of NSCs, but without altering their phenotype only in genetically modified NSCs. Modified NSCs deliver oncolytic virus to glioma more efficiently and extend survival of experimental animals in the context of radiotherapy. Our findings indicate that intranasal delivery of stem cell-based therapeutics could be optimized for future clinical applications, and allow for safe and repeated administration of biological therapies to brain tumors and other CNS disorders.

UR - http://www.scopus.com/inward/record.url?scp=84990064125&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990064125&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2016.07.024

DO - 10.1016/j.stemcr.2016.07.024

M3 - Article

C2 - 27594591

AN - SCOPUS:84990064125

SN - 2213-6711

VL - 7

SP - 471

EP - 482

JO - Stem cell reports

JF - Stem cell reports

IS - 3

ER -

Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this