ArticleInternational journal of cancer2017
Non-internalizing antibody-drug conjugates display potent anti-cancer activity upon proteolytic release of monomethyl auristatin E in the subendothelial extracellular matrix.
Article in International journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 113 citations in OpenAlex.
- Extracellular payload release from non-internalizing antibody-drug conjugates: mechanisms and linker technologies.Drug delivery · 2026Review
- From Unmet Medical Need to Drug Candidate: A Translational Therapeutic Development Roadmap Illustrated by Dual-Payload Antibody-Drug Conjugates.Biomolecules · 2026Review
- The extracellular matrix in cancer-associated fibrosis: molecular mechanisms and clinical relevance.JCI insight · 2026Review
- Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy.PLoS computational biology · 2026Article
- Targeted Therapy in Hepatobiliary Pancreatic Cancer (HPC): Advantages and Advancements of Antibody Drug Conjugates, a Type of Chemo-Biologic Hybrid Drugs.International journal of molecular sciences · 2026Review
- Self-Immolative Systems in Diagnostic and Therapeutic Applications.ChemMedChem · 2026Review
- Clinical application and optimization strategies for antibody-drug conjugates in solid tumors.The Journal of international medical research · 2026Review
- Exploring Experimental and In Silico Approaches for Antibody-Drug Conjugates in Oncology Therapies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Therapeutic challenges in HER2-targeted antibody therapies: trastuzumab and its ADC derivatives in breast cancer.American journal of cancer research · 2025Review
- Review
- Review
- The target atlas for antibody-drug conjugates across solid cancers.Cancer gene therapy · 2024Article
- Targeted Glioma Therapy-Clinical Trials and Future Directions.Pharmaceutics · 2024Review
- Diverse drug delivery systems for the enhancement of cancer immunotherapy: an overview.Frontiers in immunology · 2024Review
- Antibody-Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- G protein-coupled receptor-targeting antibody-drug conjugates: Current status and future directions.Cancer letters · 2023Review
- Visualizing Galectin-3 Binding Protein Expression with ImmunoPET.Molecular pharmaceutics · 2023Article
- Review
- Resistance to antibody-drug conjugates in breast cancer: mechanisms and solutions.Cancer communications (London, England) · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Antibody-drug conjugates (ADCs) represent a promising class of biopharmaceuticals with the potential to localize at the tumor site and improve the therapeutic index of cytotoxic drugs. While it is generally believed that ADCs need to be internalized into tumor cells in order to display optimal therapeutic activity, it has recently been shown that non-internalizing antibodies can efficiently liberate disulfide-linked drugs at the extracellular tumor site, leading to potent anti-cancer activity in preclinical animal models. Here, we show that engineered variants of the F16 antibody, specific to a splice isoform of tenascin-C, selectively localize to the subendothelial tumor extracellular matrix in three mouse models of human cancer (U87, A431, MDA-MB-231). A site-specific coupling of F16 in IgG format with a monomethyl auristatin E (MMAE) derivative, featuring a valine-citrulline dipeptide linker equipped with a self-immolative spacer, yielded an ADC product, which cured tumor-bearing mice at a dose of 7 mg/Kg. The observation of an efficient extracellular proteolytic cleavage of the valine-citrulline linker was surprising, as it has generally been assumed that this peptidic structure would be selectively cleaved by cathepsin B in intracellular compartments. The products described in this article may be useful for the treatment of human malignancies, as their cognate antigen is strongly expressed in the majority of human solid tumors, lymphomas and aggressive leukemias, while being virtually undetectable in most normal adult tissues.
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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.