ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Minimal RB-responsive E1A promoter modification to attain potency, selectivity, and transgene-arming capacity in oncolytic adenoviruses.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 73 citations in OpenAlex.
- LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001): results from arm 1 of a non-randomised, single-centre, phase 1/2 study.The Lancet. Oncology · 2024Trial
- Intravenous hyaluronidase-expressing oncolytic adenovirus with chemotherapy in metastatic pancreatic cancer: a randomized phase 2b trial.Nature medicine · 2026Article
- Oncolytic adenovirus incorporating TetO sites in the E1A promoter for controlled replication in TetR-expressing mesenchymal stem cells.Molecular therapy. Oncology · 2026Article
- LOAd703 and chemotherapy combination in pancreatic cancer: insights from the LOKON001 study.Translational gastroenterology and hepatology · 2025Article
- Synergy of oncolytic adenovirus and immune checkpoint inhibitors: transforming cancer immunotherapy paradigms.Frontiers in immunology · 2025Review
- Optimized protocol for culturing menstrual blood-derived MSCs for combination with oncolytic adenoviruses in cancer treatment.Molecular therapy. Oncology · 2024Article
- The emerging field of viroimmunotherapy for pediatric brain tumors.Neuro-oncology · 2024Review
- Article
- Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors.Journal for immunotherapy of cancer · 2022Article
- An Extensive Review on Preclinical and Clinical Trials of Oncolytic Viruses Therapy for Pancreatic Cancer.Frontiers in oncology · 2022Review
- Advances in Immunotherapies for Gliomas.Current neurology and neuroscience reports · 2022Review
- Oncolytic virus therapy in cancer: A current review.World journal of virology · 2021Review
- Stem cells for the treatment of glioblastoma: a 20-year perspective.CNS oncology · 2021Review
- Modification of Extracellular Matrix Enhances Oncolytic Adenovirus Immunotherapy in Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Microorganisms in chemotherapy for pancreatic cancer: An overview of current research and future directions.International journal of biological sciences · 2021Review
- Characterization and oncolytic virus targeting of FAP-expressing tumor-associated pericytes in glioblastoma.Acta neuropathologica communications · 2020Article
- Oncolytic Virotherapy in Glioma Tumors.International journal of molecular sciences · 2020Review
- Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome.Nanomaterials (Basel, Switzerland) · 2020Article
- Patient-derived pancreatic tumour organoids identify therapeutic responses to oncolytic adenoviruses.EBioMedicine · 2020Article
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Oncolytic adenoviruses are promising anticancer agents due to their ability to self-amplify at the tumor mass. However, tumor stroma imposes barriers difficult to overcome by these agents. Transgene expression is a valuable strategy to counteract these limitations and to enhance antitumor activity. For this purpose, the genetic backbone in which the transgene is inserted should be optimized to render transgene expression compatible with the adenovirus replication cycle and to keep genome size within the encapsidation size limit. In order to design a potent and selective oncolytic adenovirus that keeps intact all the viral functions with minimal increase in genome size, we inserted palindromic E2F-binding sites into the endogenous E1A promoter. The insertion of these sites controlling E1A-Δ24 results in a low systemic toxicity profile in mice. Importantly, the E2F-binding sites also increased the cytotoxicity and the systemic antitumor activity relative to wild-type adenovirus in all cancer models tested. The low toxicity and the increased potency results in improved antitumor efficacy after systemic injection and increased survival of mice carrying tumors. Furthermore, the constrained genome size of this backbone allows an efficient and potent expression of transgenes, indicating that this virus holds promise for overcoming the limitations of oncolytic adenoviral therapy.
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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.