ArticleMolecular cancer therapeutics2012
Dual systemic tumor targeting with ligand-directed phage and Grp78 promoter induces tumor regression.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- Advancements in research leveraging phage display technology for gastric cancer diagnosis and treatment.Frontiers in microbiology · 2025Review
- The unfolded protein response machinery in glioblastoma genesis, chemoresistance and as a druggable target.CNS neuroscience & therapeutics · 2024Review
- Construction of a bacteriophage-derived vector with potential applications in targeted drug delivery and cell imaging.Biotechnology letters · 2024Article
- Bacteriophage-based particles carrying the TNF-related apoptosis-inducing ligand (TRAIL) gene for targeted delivery in hepatocellular carcinoma.Nanoscale · 2024Article
- Review
- GRP78 Activity Moderation as a Therapeutic Treatment against Obesity.International journal of environmental research and public health · 2022Review
- Bacteriophage-Mediated Cancer Gene Therapy.International journal of molecular sciences · 2022Review
- Best of most possible worlds: Hybrid gene therapy vectors based on parvoviruses and heterologous viruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Dendrimers as Non-Viral Vectors in Gene-Directed Enzyme Prodrug Therapy.Molecules (Basel, Switzerland) · 2021Review
- Bacteriophages as Therapeutic and Diagnostic Vehicles in Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Doxorubicin Improves Cancer Cell Targeting by Filamentous Phage Gene Delivery Vectors.International journal of molecular sciences · 2020Article
- Initial Steps for the Development of a Phage-Mediated Gene Replacement Therapy Using CRISPR-Cas9 Technology.Journal of clinical medicine · 2020Article
- Engineered Bacteriophage T7 as a Potent Anticancer AgentFrontiers in microbiology · 2020Article
- Characterizing Cell Stress and GRP78 in Glioma to Enhance Tumor Treatment.Frontiers in oncology · 2020Review
- Next-generation of targeted AAVP vectors for systemic transgene delivery against cancer.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Efficacy of systemic temozolomide-activated phage-targeted gene therapy in human glioblastoma.EMBO molecular medicine · 2019Article
- Review
- CRISPR/Cas9: Transcending the Reality of Genome Editing.Molecular therapy. Nucleic acids · 2017Review
- Phage Therapy in the Era of Synthetic Biology.Cold Spring Harbor perspectives in biology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The tumor-specific Grp78 promoter is overexpressed in aggressive tumors. Cancer patients would benefit greatly from application of this promoter in gene therapy and molecular imaging; however, clinical benefit is limited by lack of strategies to target the systemic delivery of Grp78-driven transgenes to tumors. This study aims to assess the systemic efficacy of Grp78-guided expression of therapeutic and imaging transgenes relative to the standard cytomegalovirus (CMV) promoter. Combination of ligand and Grp78 transcriptional targeting into a single vector would facilitate systemic applications of the Grp78 promoter. We generated a dual tumor-targeted phage containing the arginine-glycine-aspartic acid tumor homing ligand and Grp78 promoter. Next, we combined flow cytometry, Western blot analysis, bioluminescence imaging of luciferase, and HSVtk/ganciclovir gene therapy and compared efficacy to conventional phage carrying the CMV promoter in vitro and in vivo in subcutaneous models of rat and human glioblastoma. We show that double-targeted phage provides persistent transgene expression in vitro and in tumors in vivo after systemic administration compared with conventional phage. Next, we showed significant tumor killing in vivo using the HSVtk/ganciclovir gene therapy and found a systemic antitumor effect of Grp78-driven HSVtk against therapy-resistant tumors. Finally, we uncovered a novel mechanism of Grp78 promoter activation whereby HSVtk/ganciclovir therapy upregulates Grp78 and transgene expression via the conserved unfolded protein response signaling cascade. These data validate the potential of Grp78 promoter in systemic cancer gene therapy and report the efficacy of a dual tumor targeting phage that may prove useful for translation into gene therapy and molecular imaging applications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.