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Antibody–drug conjugates: targeted weapons against cancer

Authors Iamele L, Vecchia L, Scotti C

Received 11 September 2014

Accepted for publication 22 November 2014

Published 9 January 2015 Volume 2015:5 Pages 1—13

DOI https://doi.org/10.2147/ANTI.S52914

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Professor Shixia Wang


Luisa Iamele, Luca Vecchia, Claudia Scotti

Department of Molecular Medicine, Unit of Immunology and General Pathology, University of Pavia, Pavia, PV, Italy
 
All authors contributed equally to this work

Abstract: Antibody–drug conjugates (ADCs) are formed by a targeting antibody conjugated to a chemotherapeutic molecule through a linker. Recent data demonstrate that ADCs represent a valuable advancement for the clinics and, despite their recent appearance in medicine, they are already undergoing an innovation wave aimed at targeting all three ADC building blocks. Thus, new antibody formats are being engineered, site-specific linkers are being designed, and highly toxic molecules, like RNA polymerase inhibitors, are starting to be used for conjugation. These molecules were previously considered extremely toxic and could not be used as chemotherapeutic drugs. In this review, we will present an overview of current cancer treatments and their limitations, and the logic that has led to the generation of ADCs. Their mechanism of action will be outlined, and the most recent novelties in linker design and optimization will be discussed, along with present and near future discoveries in the current ADC research pipeline.

Keywords: immunoconjugates, antibody–drug conjugates, antibody fragments, cancer, monoclonal antibodies

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