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

45 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

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

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10.1016/j.stemcr.2016.07.024

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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}",

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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

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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.

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

Abstract

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