Efficacy of systemic temozolomide-activated phage-targeted gene therapy in human glioblastoma.

EMBO Molecular Medicine
Justyna PrzystalAmin Hajitou

Abstract

Glioblastoma multiforme (GBM) is the most lethal primary intracranial malignant neoplasm in adults and most resistant to treatment. Integration of gene therapy and chemotherapy, chemovirotherapy, has the potential to improve treatment. We have introduced an intravenous bacteriophage (phage) vector for dual targeting of therapeutic genes to glioblastoma. It is a hybrid AAV/phage, AAVP, designed to deliver a recombinant adeno-associated virus genome (rAAV) by the capsid of M13 phage. In this vector, dual tumor targeting is first achieved by phage capsid display of the RGD4C ligand that binds the αvβ3 integrin receptor. Second, genes are expressed from a tumor-activated and temozolomide (TMZ)-induced promoter of the glucose-regulated protein, Grp78 Here, we investigated systemic combination therapy using TMZ and targeted suicide gene therapy by the RGD4C/AAVP-Grp78 Firstly, in vitro we showed that TMZ increases endogenous Grp78 gene expression and boosts transgene expression from the RGD4C/AAVP-Grp78 in human GBM cells. Next, RGD4C/AAVP-Grp78 targets intracranial tumors in mice following intravenous administration. Finally, combination of TMZ and RGD4C/AAVP-Grp78 targeted gene therapy exerts a synergistic effect to suppress growth...Continue Reading

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Citations

Aug 4, 2019·Proceedings of the National Academy of Sciences of the United States of America·Keittisak SuwanAmin Hajitou
Oct 20, 2020·Frontiers in Microbiology·Yoon Jung Hwang, Heejoon Myung
Oct 22, 2020·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Nicolas TournierOliver Langer
Oct 30, 2020·International Journal of Molecular Sciences·Effrosyni TsafaAmin Hajitou
Dec 29, 2020·Frontiers in Oncology·Kristie LiuFrank J Attenello
Apr 4, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aitthiphon ChongchaiAmin Hajitou
Apr 22, 2021·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Małgorzata ŁobockaAndrzej Górski
Apr 9, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Julia Fakhiri, Dirk Grimm
Jul 3, 2021·Pharmaceuticals·Bryan GibbChristine L Schneider
Sep 15, 2020·British Journal of Cancer·Motohiro NonakaMichiko N Fukuda
Dec 10, 2021·Biotechnology Journal·Abdullah K AlshememryLarry D Unsworth

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Methods Mentioned

BETA
PCR
FACS
xenografts
xenograft
Assay

Software Mentioned

ImageJ
GraphPad Prism

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