Targeting nectin-4 by antibody-drug conjugates for the treatment of urothelial carcinoma Review
| Authors: | Wong, J. L.; Rosenberg, J. E. |
| Review Title: | Targeting nectin-4 by antibody-drug conjugates for the treatment of urothelial carcinoma |
| Abstract: | Introduction: Nectin-4 is a tumor-associated antigen overexpressed in urothelial carcinoma and several other malignancies. It has emerged as a compelling target for novel tumor-directed therapies, particularly as a component of antibody-drug conjugates (ADCs), a growing class of anti-cancer therapeutic agents. Development of nectin-4-directed therapies has been led by enfortumab vedotin (EV), an ADC comprised of a fully human monoclonal antibody specific for nectin-4 conjugated via a cleavable linker to the microtubule inhibitor MMAE. EV was approved in 2019 as a first-in-class agent for the treatment of urothelial carcinoma. Areas covered: This article discusses general principles relevant to ADC design and our current understanding of nectin-4 in normal physiology and malignancy, followed by a review of the development of EV as well as additional drug conjugate strategies targeting nectin-4. Expert opinion: EV offers proof-of-concept for the clinical utility of nectin-4-directed therapies and provides further support for ADCs as an important class of anti-cancer agents. Future development of nectin-4-targeted approaches will benefit from a deeper understanding of nectin-4 biology in both health and disease, as well as a detailed exploration of the mechanisms underlying therapeutic activity and resistance. © 2021 Informa UK Limited, trading as Taylor & Francis Group. |
| Keywords: | urothelial carcinoma; antibody-drug conjugates; nectin-4; enfortumab vedotin |
| Journal Title: | Expert Opinion on Biological Therapy |
| Volume: | 21 |
| Issue: | 7 |
| ISSN: | 1471-2598 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2021-01-01 |
| Start Page: | 863 |
| End Page: | 873 |
| Language: | English |
| DOI: | 10.1080/14712598.2021.1929168 |
| PUBMED: | 34030536 |
| PROVIDER: | scopus |
| PMCID: | PMC8224177 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 1 July 2021 -- Source: Scopus |
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