ArticleBioconjugate chemistry2017
Protease-Cleavable Linkers Modulate the Anticancer Activity of Noninternalizing Antibody-Drug Conjugates.
Article in Bioconjugate chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 84 citations in OpenAlex.
- Extracellular payload release from non-internalizing antibody-drug conjugates: mechanisms and linker technologies.Drug delivery · 2026Review
- Cancer-associated alterations in O-GalNAc glycosylation.Glycobiology · 2026Review
- STING Agonist-Loaded Physalis Mottle Virus-like Particles as a Potent Prophylactic for Metastatic Melanoma.ACS applied materials & interfaces · 2025Article
- Targeting oncofetal fibronectin and neuropilin-1 in solid tumors with PL2 peptide.Scientific reports · 2025Article
- Peptide-Drug Conjugates: A New Hope for Cancer.Journal of peptide science : an official publication of the European Peptide Society · 2025Review
- Innovative Peptide Therapeutics in the Pipeline: Transforming Cancer Detection and Treatment.International journal of molecular sciences · 2025Review
- Unlocking the Complexity of Antibody-Drug Conjugates: A Cutting-Edge LC-HRMS Approach to Refine Drug-to-Antibody Ratio Measurements with Highly Reactive Payloads.International journal of molecular sciences · 2025Article
- Tracking the Fate of Therapeutic Proteins Using Ratiometric Imaging of Responsive Shortwave Infrared Probes.Journal of the American Chemical Society · 2025Article
- Quorum Sensing Inhibitors: An Alternative Strategy to Win the Battle against Multidrug-Resistant (MDR) Bacteria.Molecules (Basel, Switzerland) · 2024Review
- Stimuli-sensitive polymer prodrug nanocarriers by reversible-deactivation radical polymerization.Chemical Society reviews · 2024Review
- Review
- Antibody Drug Conjugates in Bladder Cancer: Current Milestones and Future Perspectives.Current treatment options in oncology · 2023Review
- Antibody-Drug Conjugate Sacituzumab Govitecan Drives Efficient Tissue Penetration and Rapid Intracellular Drug Release.Molecular cancer therapeutics · 2023Article
- Article
- Optimizing the enzymatic release of MMAE fromFrontiers in pharmacology · 2023Article
- Anti-Extra Domain B Splice Variant of Fibronectin Antibody-Drug Conjugate Eliminates Tumors with Enhanced Efficacy When Combined with Checkpoint Blockade.Molecular cancer therapeutics · 2022Article
- A Novel NAMPT Inhibitor-Based Antibody-Drug Conjugate Payload Class for Cancer Therapy.Bioconjugate chemistry · 2022Article
- Monitoring In Vivo Performances of Protein-Drug Conjugates Using Site-Selective Dual Radiolabeling and Ex Vivo Digital Imaging.Journal of medicinal chemistry · 2022Article
- Therapeutic antibodies - natural and pathological barriers and strategies to overcome them.Pharmacology & therapeutics · 2022Review
- PL1 Peptide Engages Acidic Surfaces on Tumor-Associated Fibronectin and Tenascin Isoforms to Trigger Cellular Uptake.Pharmaceutics · 2021Article
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 an attractive class of biopharmaceutical agents, with the potential to selectively deliver potent cytotoxic agents to tumors. It is generally assumed that ADC products should preferably bind and internalize into cancer cells in order to liberate their toxic payload, but a growing body of evidence indicates that also ADCs based on noninternalizing antibodies may be potently active. In this Communication, we investigated dipeptide-based linkers (frequently used for internalizing ADC products) in the context of the noninternalizing F16 antibody, specific to a splice isoform of tenascin-C. Using monomethyl auristatin E (MMAE) as potent cytotoxic drug, we observed that a single amino acid substitution of the Val-Cit dipeptide linker can substantially modulate the in vivo stability of the corresponding ADC products, as well as the anticancer activity in mice bearing the human epidermoid A431 carcinoma. In these settings, the linker based on the Val-Ala dipeptide exhibited better performances, compared to Val-Cit, Val-Lys, and Val-Arg analogues. Mass spectrometric analysis revealed that the four linkers displayed not only different stability in vivo but also differences in cleavage sites. Moreover, the absence of anticancer activity for a F16-MMAE conjugate featuring a noncleavable linker indicated that drug release modalities, based on proteolytic degradation of the immunoglobulin moiety, cannot be exploited with noninternalizing antibodies. ADC products based on the noninternalizing F16 antibody may be useful for the treatment of several human malignancies, as the cognate antigen is abundantly expressed in the extracellular matrix of several tumors, 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.