ArticleMolecular cancer therapeutics2009
A heterotypic bystander effect for tumor cell killing after adeno-associated virus/phage-mediated, vascular-targeted suicide gene transfer.
Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 52 citations in OpenAlex.
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- Bacteriophage-Mediated Cancer Gene Therapy.International journal of molecular sciences · 2022Review
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- Efficacy of systemic temozolomide-activated phage-targeted gene therapy in human glioblastoma.EMBO molecular medicine · 2019Article
- Drug delivery vectors based on filamentous bacteriophages and phage-mimetic nanoparticles.Drug delivery · 2017Review
- Mind the Gaps in Tumor Immunity: Impact of Connexin-Mediated Intercellular Connections.Frontiers in immunology · 2017Review
- Targeted molecular-genetic imaging and ligand-directed therapy in aggressive variant prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Sindbis Virus-Pseudotyped Lentiviral Vectors Carrying VEGFR2-Specific Nanobody for Potential Transductional Targeting of Tumor Vasculature.Molecular biotechnology · 2016Article
- Ligand-targeted theranostic nanomedicines against cancer.Journal of controlled release : official journal of the Controlled Release Society · 2016Review
- Phage Therapy in the Era of Synthetic Biology.Cold Spring Harbor perspectives in biology · 2016Review
- The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction.Oncotarget · 2016Article
- AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Modulation of extracellular matrix in cancer is associated with enhanced tumor cell targeting by bacteriophage vectors.Molecular cancer · 2015Article
- Adeno-associated virus-mediated cancer gene therapy: current status.Cancer letters · 2015Review
- Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Suicide gene transfer is the most commonly used cytotoxic approach in cancer gene therapy; however, a successful suicide gene therapy depends on the generation of efficient targeted systemic gene delivery vectors. We recently reported that selective systemic delivery of suicide genes such as herpes simplex virus thymidine kinase (HSVtk) to tumor endothelial cells through a novel targeted adeno-associated virus/phage vector leads to suppression of tumor growth. This marked effect has been postulated to result primarily from the death of cancer cells by hypoxia following the targeted disruption of tumor blood vessels. Here, we investigated whether an additional mechanism of action is involved. We show that there is a heterotypic "bystander" effect between endothelial cells expressing the HSVtk suicide gene and tumor cells. Treatment of cocultures of HSVtk-transduced endothelial cells and non-HSVtk-transduced tumor cells with ganciclovir results in the death of both endothelial and tumor cells. Blocking of this effect by 18alpha-glycyrrhetinic acid indicates that gap junctions between endothelial and tumor cells are largely responsible for this phenomenon. Moreover, the observed bystander killing is mediated by connexins 43 and 26, which are expressed in endothelial and tumor cell types. Finally, this heterotypic bystander effect is accompanied by a suppression of tumor growth in vivo that is independent of primary gene transfer into host-derived tumor vascular endothelium. These findings add an alternative nonmutually exclusive and potentially synergistic cytotoxic mechanism to cancer gene therapy based on targeted adeno-associated virus/phage and further support the promising role of nonmalignant tumor stromal cells as therapeutic targets.
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