ArticleScientific reports2019
Unravelling Receptor and RGD Motif Dependence of Retargeted Adenoviral Vectors using Advanced Tumor Model Systems.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Retargeted adenoviruses for local IgA and CD47 blocker production as a novel cancer therapy.EMBO molecular medicine · 2026Article
- Nanomedicine in Cancer Therapeutics: Current Perspectives from Bench to Bedside.Molecular cancer · 2025Review
- Organ-on-a-chip models for development of cancer immunotherapies.Cancer immunology, immunotherapy : CII · 2023Review
- Potent and selective eradication of tumor cells by an EpCAM-targeted Ras-degrading enzyme.Molecular therapy oncolytics · 2023Article
- Article
- Mimicking the Biology of Engineered Protein and mRNA Nanoparticle Delivery Using a Versatile Microfluidic Platform.Pharmaceutics · 2021Article
- The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal.Pharmaceutics · 2021Review
- Step-by-Step Immune Activation for Suicide Gene Therapy Reinforcement.International journal of molecular sciences · 2021Review
- A Hybrid In Silico and Tumor-on-a-Chip Approach to Model Targeted Protein Behavior in 3D Microenvironments.Cancers · 2021Article
- A Computational Investigation of In Vivo Cytosolic Protein Delivery for Cancer Therapy.Pharmaceutics · 2021Article
- Reengineering anthrax toxin protective antigen for improved receptor-specific protein delivery.BMC biology · 2020Article
- Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent advances in engineering adenoviruses are paving the way for new therapeutic gene delivery approaches in cancer. However, there is limited knowledge regarding the impact of adenoviral retargeting on transduction efficiency in more complex tumor architectures, and the role of the RGD loop at the penton base in retargeting is unclear. To address this gap, we used tumor models of increasing complexity to study the role of the receptor and the RGD motif. Employing tumor-fibroblast co-culture models, we demonstrate the importance of the RGD motif for efficient transduction in 2D through the epithelial cell adhesion molecule (EpCAM), but not the epidermal growth factor receptor (EGFR). Via optical clearing of co-culture spheroids, we show that the RGD motif is required for transduction via both receptors in 3D tumor architectures. We subsequently employed a custom-designed microfluidic model containing collagen-embedded tumor spheroids, mimicking the interplay between interstitial flow, extracellular matrix and adenoviral transduction. Image analysis of on-chip cleared spheroids indicated the importance of the RGD motif for on-chip adenoviral transduction. Together, our results show the interrelationship between receptor characteristics, the RGD motif, the 3D tumor architecture and retargeted adenoviral transduction efficiency. The findings are important for the rational design of next-generation therapeutic adenoviruses.
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