Antibody-Drug Conjugates for Tumor Targeting-Novel Conjugation Chemistries and the Promise of non-IgG Binding Proteins

Merten, Hannes; Brandl, Fabian; Plückthun, Andreas; Zangemeister-Wittke, Uwe (2015). Antibody-Drug Conjugates for Tumor Targeting-Novel Conjugation Chemistries and the Promise of non-IgG Binding Proteins. Bioconjugate chemistry, 26(11), pp. 2176-2185. American Chemical Society 10.1021/acs.bioconjchem.5b00260

[img] Text
Antibody−Drug Conjugates for Tumor TargetingNovel.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy
[img]
Preview
Text
Merten et al. 2015.pdf - Accepted Version
Available under License Publisher holds Copyright.

Download (308kB) | Preview

Antibody-drug conjugates (ADCs) have emerged as a promising class of anticancer agents, combining the specificity of antibodies for tumor targeting and the destructive potential of highly potent drugs as payload. An essential component of these immunoconjugates is a bifunctional linker capable of reacting with the antibody and the payload to assemble a functional entity. Linker design is fundamental, as it must provide high stability in the circulation to prevent premature drug release, but be capable of releasing the active drug inside the target cell upon receptor-mediated endocytosis. Although ADCs have demonstrated an increased therapeutic window, compared to conventional chemotherapy in recent clinical trials, therapeutic success rates are still far from optimal. To explore other regimes of half-life variation and drug conjugation stoichiometries, it is necessary to investigate additional binding proteins which offer access to a wide range of formats, all with molecularly defined drug conjugation. Here, we delineate recent progress with site-specific and biorthogonal conjugation chemistries, and discuss alternative, biophysically more stable protein scaffolds like Designed Ankyrin Repeat Proteins (DARPins), which may provide such additional engineering opportunities for drug conjugates with improved pharmacological performance.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Brandl, Fabian and Zangemeister-Wittke, Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1043-1802

Publisher:

American Chemical Society

Language:

English

Submitter:

Debora Scherrer

Date Deposited:

22 Feb 2016 17:14

Last Modified:

10 Sep 2017 15:27

Publisher DOI:

10.1021/acs.bioconjchem.5b00260

PubMed ID:

26086208

BORIS DOI:

10.7892/boris.76796

URI:

https://boris.unibe.ch/id/eprint/76796

Actions (login required)

Edit item Edit item
Provide Feedback