Issue 1, 2013

Spacer length shapes drug release and therapeutic efficacy of traceless disulfide-linked ADCs targeting the tumor neovasculature

Abstract

We systematically investigated how the therapeutic efficacy of a traceless, vascular targeting antibody–drug conjugate (ADC) is affected by the length of a spacer introduced between the antibody's globular fold and the site of drug attachment. Homogeneous ADCs were prepared from the direct conjugation of engineered C-terminal cysteines with a potent thiol containing drug which was separated from the antibody surface by unstructured spacers of increasing length. We found that a smaller spacer length is reflected in enhanced stability and therapeutic efficacy of the conjugates in a syngeneic model of murine cancer.

Graphical abstract: Spacer length shapes drug release and therapeutic efficacy of traceless disulfide-linked ADCs targeting the tumor neovasculature

Supplementary files

Article information

Article type
Edge Article
Submitted
28 Jul 2012
Accepted
05 Oct 2012
First published
08 Oct 2012

Chem. Sci., 2013,4, 297-302

Spacer length shapes drug release and therapeutic efficacy of traceless disulfide-linked ADCs targeting the tumor neovasculature

M. Steiner, I. Hartmann, E. Perrino, G. Casi, S. Brighton, I. Jelesarov, G. J. L. Bernardes and D. Neri, Chem. Sci., 2013, 4, 297 DOI: 10.1039/C2SC21107F

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements