# Chemically triggered drug release from an antibody-drug conjugate leads to potent antitumour activity in mice

Article · Rossin R, Versteegen RM, Wu J, Khasanov A, Wessels HJ, Steenbergen EJ, Ten Hoeve W, Janssen HM, van Onzen AHAM, Hudson PJ, Robillard MS

- Archive id: doi:10.1038/s41467-018-03880-y
- Published: 2018-05-04
- Venue: Nature communications
- DOI: https://doi.org/10.1038/s41467-018-03880-y
- PMID: 29728559
- PMCID: PMC5935733
- Citations: 215
- Source URL: https://doi.org/10.1038/s41467-018-03880-y
- PDF: https://europepmc.org/articles/PMC5935733/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Cancer Immunotherapy](https://space-kitty.com/topics/cancer-immunotherapy)

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