ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Adenovirus i-leader truncation bioselected against cancer-associated fibroblasts to overcome tumor stromal barriers.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Potency-enhancing mutations in E3-19K and i-leader increase the cytolytic activity of the PH20/Molecular therapy. Oncology · 2026Article
- Exosomal microRNAs: A new role in the diagnosis and treatment of lung cancer metastases (Review).International journal of oncology · 2025Review
- Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).International journal of molecular medicine · 2025Review
- The implications of oncolytic viruses targeting fibroblasts in enhancing the antitumoural immune response.Heliyon · 2024Review
- Oncolytic adenovirus: A tool for reversing the tumor microenvironment and promoting cancer treatment (Review).Oncology reports · 2021Review
- Germline mutations and blood malignancy (Review).Oncology reports · 2021Review
- Experimental virus evolution in cancer cell monolayers, spheroids, and tissue explants.Virus evolution · 2021Article
- Strategies to Develop Potent Oncolytic Viruses and Enhance Their Therapeutic Efficacy.JCO precision oncology · 2021Review
- Simultaneous Tumor and Stroma Targeting by Oncolytic Viruses.Biomedicines · 2020Review
- Bioselection Reveals miR-99b and miR-485 as Enhancers of Adenoviral Oncolysis in Pancreatic Cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- RGD-modified oncolytic adenovirus-harboring shPKM2 exhibits a potent cytotoxic effect in pancreatic cancer via autophagy inhibition and apoptosis promotion.Cell death & disease · 2017Article
- The 5'UTR in human adenoviruses: leader diversity in late gene expression.Scientific reports · 2017Article
- Mesenchymal Stromal Cells for Linked Delivery of Oncolytic and Apoptotic Adenoviruses to Non-small-cell Lung Cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Article
- iRGD tumor-penetrating peptide-modified oncolytic adenovirus shows enhanced tumor transduction, intratumoral dissemination and antitumor efficacy.Gene therapy · 2014Article
- Oncolytic Adenoviruses in Cancer Treatment.Biomedicines · 2014Review
- The combination of i-leader truncation and gemcitabine improves oncolytic adenovirus efficacy in an immunocompetent model.Cancer gene therapy · 2014Article
- The Antiviral Effect of High-Molecular Weight Poly-Gamma-Glutamate against Newcastle Disease Virus on Murine Macrophage Cells.Advances in virology · 2014Article
- Adeno-associated virus enhances wild-type and oncolytic adenovirus spread.Human gene therapy methods · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor-associated stromal cells constitute a major hurdle in the antitumor efficacy with oncolytic adenoviruses. To overcome this biological barrier, an in vitro bioselection of a mutagenized AdwtRGD stock in human cancer-associated fibroblasts (CAFs) was performed. Several rounds of harvest at early cytopathic effect (CPE) followed by plaque isolation led us to identify one mutant with large plaque phenotype, enhanced release in CAFs and enhanced cytotoxicity in CAF and several tumor cell lines. Whole genome sequencing and functional mapping identified the truncation of the last 17 amino acids in C-terminal end of the i-leader protein as the mutation responsible for this phenotype. Similar mutations have been previously isolated in two independent bioselection processes in tumor cell lines. Importantly, our results establish the enhanced antitumor activity in vivo of the i-leader C-terminal truncated mutants, especially in a desmotic fibroblast-embedded lung carcinoma model in mice. These results indicate that the i-leader truncation represents a promising trait to improve virotherapy with oncolytic adenoviruses.
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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.