ArticlePloS one2014
Identification of a new epitope in uPAR as a target for the cancer therapeutic monoclonal antibody ATN-658, a structural homolog of the uPAR binding integrin CD11b (αM).
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 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
23 citing papers in PubMed, 39 citations in OpenAlex.
- uPAR deficiency triggers TGFβ1-mediated fibrotic remodeling in a cardiac perivascular-like microenvironment.Stem cell research & therapy · 2026Article
- uPAR-directed immunotherapies in solid tumors: current advances and future perspectives.Frontiers in pharmacology · 2026Review
- Pro-Angiogenic Bioactive Molecules in Vascular Morphogenesis: Integrating Endothelial Cell Dynamics.Current issues in molecular biology · 2025Review
- Review
- uPAR Immuno-PET in Pancreatic Cancer, Aging, and Chemotherapy-Induced Senescence.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2024Article
- Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity.Clinical and translational allergy · 2023Article
- suPAR: An Inflammatory Mediator for Kidneys.Kidney diseases (Basel, Switzerland) · 2022Review
- Therapeutic strategies targeting uPAR potentiate anti-PD-1 efficacy in diffuse-type gastric cancer.Science advances · 2022Article
- Review
- Transcriptome and proteome profiling of activated cardiac fibroblasts supports target prioritization in cardiac fibrosis.Frontiers in cardiovascular medicine · 2022Article
- Further Understanding of Urokinase Plasminogen Activator Overexpression in Urothelial Bladder Cancer Progression, Clinical Outcomes and Potential Therapeutic Targets.OncoTargets and therapy · 2021Review
- Molecular imaging of the urokinase plasminogen activator receptor: opportunities beyond cancer.EJNMMI research · 2020Review
- uPAR antibody (huATN-658) and Zometa reduce breast cancer growth and skeletal lesions.Bone research · 2020Article
- Structural Biology and Protein Engineering of Thrombolytics.Computational and structural biotechnology journal · 2019Review
- Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications.Frontiers in oncology · 2018Review
- Transcriptomic pathway analysis of urokinase receptor silenced breast cancer cells: a microarray study.Oncotarget · 2017Article
- uPAR directed-imaging of head-and-neck cancer.Oncotarget · 2017Article
- Urokinase type plasminogen activator receptor (uPAR) as a new therapeutic target in cancer.Translational medicine @ UniSa · 2016Article
- Mapping the topographic epitope landscape on the urokinase plasminogen activator receptor (uPAR) by surface plasmon resonance and X-ray crystallography.Data in brief · 2015Article
- uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery.Oncotarget · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
The urokinase plasminogen activator receptor (uPAR) plays a role in tumor progression and has been proposed as a target for the treatment of cancer. We recently described the development of a novel humanized monoclonal antibody that targets uPAR and has anti-tumor activity in multiple xenograft animal tumor models. This antibody, ATN-658, does not inhibit ligand binding (i.e. uPA and vitronectin) to uPAR and its mechanism of action remains unclear. As a first step in understanding the anti-tumor activity of ATN-658, we set out to identify the epitope on uPAR to which ATN-658 binds. Guided by comparisons between primate and human uPAR, epitope mapping studies were performed using several orthogonal techniques. Systematic site directed and alanine scanning mutagenesis identified the region of aa 268-275 of uPAR as the epitope for ATN-658. No known function has previously been attributed to this epitope Structural insights into epitope recognition were obtained from structural studies of the Fab fragment of ATN-658 bound to uPAR. The structure shows that the ATN-658 binds to the DIII domain of uPAR, close to the C-terminus of the receptor, corroborating the epitope mapping results. Intriguingly, when bound to uPAR, the complementarity determining region (CDR) regions of ATN-658 closely mimic the binding regions of the integrin CD11b (αM), a previously identified uPAR ligand thought to be involved in leukocyte rolling, migration and complement fixation with no known role in tumor progression of solid tumors. These studies reveal a new functional epitope on uPAR involved in tumor progression and demonstrate a previously unrecognized strategy for the therapeutic targeting of uPAR.
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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.