Antibody–Drug Conjugates: An Emerging Concept in Cancer Therapy
Top Cited Papers
- 20 February 2014
- journal article
- review article
- Published by Wiley in Angewandte Chemie-International Edition
- Vol. 53 (15), 3796-3827
- https://doi.org/10.1002/anie.201307628
Abstract
Traditional cancer chemotherapy is often accompanied by systemic toxicity to the patient. Monoclonal antibodies against antigens on cancer cells offer an alternative tumor‐selective treatment approach. However, most monoclonal antibodies are not sufficiently potent to be therapeutically active on their own. Antibody–drug conjugates (ADCs) use antibodies to deliver a potent cytotoxic compound selectively to tumor cells, thus improving the therapeutic index of chemotherapeutic agents. The recent approval of two ADCs, brentuximab vedotin and ado‐trastuzumab emtansine, for cancer treatment has spurred tremendous research interest in this field. This Review touches upon the early efforts in the field, and describes how the lessons learned from the first‐generation ADCs have led to improvements in every aspect of this technology, i.e., the antibody, the cytotoxic compound, and the linker connecting them, leading to the current successes. The design of ADCs currently in clinical development, and results from mechanistic studies and preclinical and clinical evaluation are discussed. Emerging technologies that seek to further advance this exciting area of research are also discussed.Keywords
This publication has 101 references indexed in Scilit:
- Synthesis of site-specific antibody-drug conjugates using unnatural amino acidsProceedings of the National Academy of Sciences of the United States of America, 2012
- Influence of Affinity and Antigen Internalization on the Uptake and Penetration of Anti-HER2 Antibodies in Solid TumorsCancer Research, 2011
- Design of Antibody−Maytansinoid Conjugates Allows for Efficient Detoxification via Liver MetabolismBioconjugate Chemistry, 2011
- Microtubule-binding agents: a dynamic field of cancer therapeuticsNature Reviews Drug Discovery, 2010
- SG2285, a Novel C2-Aryl-Substituted Pyrrolobenzodiazepine Dimer Prodrug That Cross-links DNA and Exerts Highly Potent Antitumor ActivityCancer Research, 2010
- CEACAM5-Targeted Therapy of Human Colonic and Pancreatic Cancer Xenografts with Potent Labetuzumab-SN-38 ImmunoconjugatesClinical Cancer Research, 2009
- Antibody Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN-38) for Targeted Cancer ChemotherapyJournal of Medicinal Chemistry, 2008
- Anti-CD30 diabody-drug conjugates with potent antitumor activityMolecular Cancer Therapeutics, 2008
- Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic indexNature Biotechnology, 2008
- ISOLATION AND BEHAVIOR OF SPIRO[2,5]OCTA-1,4-DIENE-3-ONEJournal of the American Chemical Society, 1957