dc.contributor.author | Przystal, JM | |
dc.contributor.author | Waramit, S | |
dc.contributor.author | Pranjol, MZI | |
dc.contributor.author | Yan, W | |
dc.contributor.author | Chu, G | |
dc.contributor.author | Chongchai, A | |
dc.contributor.author | Samarth, G | |
dc.contributor.author | Olaciregui, NG | |
dc.contributor.author | Tabatabai, G | |
dc.contributor.author | Carcaboso, AM | |
dc.contributor.author | Aboagye, EO | |
dc.contributor.author | Suwan, K | |
dc.contributor.author | Hajitou, A | |
dc.date.accessioned | 2019-03-14T17:14:58Z | |
dc.date.available | 2019-03-14T17:14:58Z | |
dc.date.issued | 2019-02-26 | |
dc.identifier.citation | Przystal, J. M., et al. (2019). "Efficacy of systemic temozolomide‐activated phage‐targeted gene therapy in human glioblastoma." EMBO Molecular Medicine: e8492. | en_US |
dc.identifier.issn | 1757-4676 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/56232 | |
dc.description.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 of orthotopic glioblastoma. | en_US |
dc.description.sponsorship | . This study was supported by a grant G0701159 of the UK Medical Research Council (MRC) and the Brain Tumour Research Campaign (BTRC). Keittisak Suwan is funded by the Children with Cancer UK (13/147 and 16/230). AMC is funded by ISCIII-FEDER (CP13/00189). JP received a stipend from the BTRC. EOA acknowledges support from Imperial College NIHR Biomedical Research Centre award (WSCC_P62585), Cancer Research UK grant (C2536/A16584), Medical Research Council grant (MC-A652- 5PY80), and Experimental Cancer Medicine Centres grant (C37/A7283). | en_US |
dc.language | eng | |
dc.language.iso | en | en_US |
dc.publisher | Wiley-VCH Verlag | en_US |
dc.relation.ispartof | EMBO Mol Med | |
dc.rights | Creative Commons Attribution | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | Grp78 | en_US |
dc.subject | bacteriophage | en_US |
dc.subject | glioblastoma | en_US |
dc.subject | targeting | en_US |
dc.subject | temozolomide | en_US |
dc.title | Efficacy of systemic temozolomide-activated phage-targeted gene therapy in human glioblastoma. | en_US |
dc.type | Article | en_US |
dc.rights.holder | 2019 The Authors | |
dc.identifier.doi | 10.15252/emmm.201708492 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/30808679 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |