ArticleCell death & disease2012
Superior antitumoral activity of dimerized targeted single-chain TRAIL fusion proteins under retention of tumor selectivity.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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.
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Who cites it
29 citing papers in PubMed, 67 citations in OpenAlex.
- Comparison of antibody-scTRAIL Fc fusion proteins with varying valency for EGFR and TRAIL receptors.Scientific reports · 2025Article
- Beyond ADCs: harnessing bispecific antibodies to directly induce apoptosis for targeted tumor eradication.Antibody therapeutics · 2024Review
- Design and Synthesis of DNA Origami Nanostructures to Control TNF Receptor Activation.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Mapping tissue heterogeneity in solid tumours using PET-MRI and machine learning.Nature biomedical engineering · 2023Article
- Quantification of intratumoural heterogeneity in mice and patients via machine-learning models trained on PET-MRI data.Nature biomedical engineering · 2023Article
- The benefits of clustering in TNF receptor superfamily signaling.Frontiers in immunology · 2023Review
- Low-Level Endothelial TRAIL-Receptor Expression Obstructs the CNS-Delivery of Angiopep-2 Functionalised TRAIL-Receptor Agonists for the Treatment of Glioblastoma.Molecules (Basel, Switzerland) · 2021Article
- Influence of antigen density and immunosuppressive factors on tumor-targeted costimulation with antibody-fusion proteins and bispecific antibody-mediated T cell response.Cancer immunology, immunotherapy : CII · 2020Article
- Article
- Molecular Mode of Action of TRAIL Receptor Agonists-Common Principles and Their Translational Exploitation.Cancers · 2019Review
- Diabody-Ig: a novel platform for the generation of multivalent and multispecific antibody molecules.mAbs · 2019Article
- Importance of TRAIL Molecular Anatomy in Receptor Oligomerization and Signaling. Implications for Cancer Therapy.Cancers · 2019Review
- IgG-single-chain TRAIL fusion proteins for tumour therapy.Scientific reports · 2018Article
- Pro-apoptotic effect of TRAIL-transfected endothelial progenitor cells on glioma cells.Oncology letters · 2018Article
- Targeting scFv-Fc-scTRAIL fusion proteins to tumor cells.Oncotarget · 2018Article
- Article
- Antibodies and Derivatives Targeting DR4 and DR5 for Cancer Therapy.Antibodies (Basel, Switzerland) · 2017Review
- Antitumor Activity of a Mesenchymal Stem Cell Line Stably Secreting a Tumor-Targeted TNF-Related Apoptosis-Inducing Ligand Fusion Protein.Frontiers in immunology · 2017Article
- A novel capsid-modified oncolytic recombinant adenovirus type 5 for tumor-targeting gene therapy by intravenous route.Oncotarget · 2016Article
- Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although targeting of the death receptors (DRs) DR4 and DR5 still appears a suitable antitumoral strategy, the limited clinical responses to recombinant soluble TNF-related apoptosis inducing ligand (TRAIL) necessitate novel reagents with improved apoptotic activity/tumor selectivity. Apoptosis induction by a single-chain TRAIL (scTRAIL) molecule could be enhanced >10-fold by generation of epidermal growth factor receptor (EGFR)-specific scFv-scTRAIL fusion proteins. By forcing dimerization of scFv-scTRAIL based on scFv linker modification, we obtained a targeted scTRAIL composed predominantly of dimers (Db-scTRAIL), exceeding the activity of nontargeted scTRAIL ∼100-fold on Huh-7 hepatocellular and Colo205 colon carcinoma cells. Increased activity of Db-scTRAIL was also demonstrated on target-negative cells, suggesting that, in addition to targeting, oligomerization equivalent to an at least dimeric assembly of standard TRAIL per se enhances apoptosis signaling. In the presence of apoptosis sensitizers, such as the proteasomal inhibitor bortezomib, Db-scTRAIL was effective at picomolar concentrations in vitro (EC(50) ∼2 × 10(-12) M). Importantly, in vivo, Db-scTRAIL was well tolerated and displayed superior antitumoral activity in mouse xenograft (Colo205) tumor models. Our results show that both targeting and controlled dimerization of scTRAIL fusion proteins provides a strategy to enforce apoptosis induction, together with retained tumor selectivity and good in vivo tolerance.
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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.