{"id":"doi:10.1038/s41467-018-03880-y","kind":"article","title":"Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice","authors":["Rossin R","Versteegen RM","Wu J","Khasanov A","Wessels HJ","Steenbergen EJ","Ten Hoeve W","Janssen HM","van Onzen AHAM","Hudson PJ","Robillard MS"],"author_count":11,"year":2018,"published":"2018-05-04","venue":"Nature communications","cited_by":215,"doi":"10.1038/s41467-018-03880-y","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-018-03880-y","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-018-03880-y","updated":null,"pmid":"29728559","pmcid":"PMC5935733","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5935733/pdf","abstract":"Current antibody-drug conjugates (ADCs) target internalising receptors on cancer cells leading to intracellular drug release. Typically, only a subset of patients with solid tumours has sufficient expression of such a receptor, while there are suitable non-internalising receptors and stroma targets. Here, we demonstrate potent therapy in murine tumour models using a non-internalising ADC that releases its drugs upon a click reaction with a chemical activator, which is administered in a second step. This was enabled by the development of a diabody-based ADC with a high tumour uptake and very low retention in healthy tissues, allowing systemic administration of the activator 2 days later, leading to efficient and selective activation throughout the tumour. In contrast, the analogous ADC comprising the protease-cleavable linker used in the FDA approved ADC Adcetris is not effective in these tumour models. This first-in-class ADC holds promise for a broader applicability of ADCs across patient populations.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice\" by Rossin R, Versteegen RM, Wu J et al., https://doi.org/10.1038/s41467-018-03880-y, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"cancer-immunotherapy","name":"Cancer Immunotherapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}