Header

UZH-Logo

Maintenance Infos

A non-internalizing antibody-drug conjugate based on an anthracycline payload displays potent therapeutic activity in vivo


Dal Corso, Alberto; Gébleux, Rémy; Murer, Patrizia; Soltermann, Alex; Neri, Dario (2017). A non-internalizing antibody-drug conjugate based on an anthracycline payload displays potent therapeutic activity in vivo. Journal of Controlled Release, 264:211-218.

Abstract

Antibody-drug conjugates are generally believed to crucially rely on internalization into cancer cells for therapeutic activity. Here, we show that a non-internalizing antibody-drug conjugate, based on the F16 antibody specific to the alternatively spliced A1 domain of tenascin-C, mediates a potent therapeutic activity when equipped with the anthracycline PNU159682. The peptide linker, connecting the F16 antibody in IgG format at a specific cysteine residue to the drug, was stable in serum but could be efficiently cleaved in the subendothelial extracellular matrix by proteases released by the dying tumor cells. The results indicate that there may be a broader potential applicability of non-internalizing antibody-drug conjugates for cancer therapy than what had previously been assumed.

Abstract

Antibody-drug conjugates are generally believed to crucially rely on internalization into cancer cells for therapeutic activity. Here, we show that a non-internalizing antibody-drug conjugate, based on the F16 antibody specific to the alternatively spliced A1 domain of tenascin-C, mediates a potent therapeutic activity when equipped with the anthracycline PNU159682. The peptide linker, connecting the F16 antibody in IgG format at a specific cysteine residue to the drug, was stable in serum but could be efficiently cleaved in the subendothelial extracellular matrix by proteases released by the dying tumor cells. The results indicate that there may be a broader potential applicability of non-internalizing antibody-drug conjugates for cancer therapy than what had previously been assumed.

Statistics

Altmetrics

Downloads

2 downloads since deposited on 08 Dec 2017
2 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Anthracyclines; Antibodies; Antibody-drug conjugates; Protein engineering; Vascular targeting
Language:English
Date:28 October 2017
Deposited On:08 Dec 2017 16:25
Last Modified:08 Dec 2017 17:26
Publisher:Elsevier
ISSN:0168-3659
Publisher DOI:https://doi.org/10.1016/j.jconrel.2017.08.040
PubMed ID:28867376

Download