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Nectin-4-directed antibody-drug conjugates (ADCs): Spotlight on preclinical and clinical evidence
Mohammad Javad Khosravanian1, Yousef Mirzaei2, Ali Hussein Mer3
1Student Research Committee, Larestan University of Medical Sciences, Larestan, Iran.
Abstract:
Nectin-4 (Nectin cell adhesion molecule 4), a type I transmembrane cell adhesion protein, was demonstrated to be overexpressed in a variety of tumors, making it an attractive antigen for targeted therapies such as antibody-drug conjugates (ADCs). Of great note, the US Food and Drug Administration (FDA)-approval of the first Nectin-4-directed ADC, enfortumab vedotin (EV), in urothelial cancer (UC) not only introduced Nectin-4 as a clinically validated and reliable target antigen but also confirmed the evolving role of Nectin-4-directed ADCs as novel and promising cancer therapeutics. In addition to EV, there have been or are currently being seven and eleven Nectin-4-directed ADCs, respectively, in various stages of clinical trials and preclinical development, offering a promising future for the treatment of Nectin-4-positive cancer patients. This study reviewed clinical- and preclinical-stage Nectin-4-directed ADCs.
Insights
Nectin-4 is a validated cancer target, with approved antibody-drug conjugates (ADCs) like enfortumab vedotin showing promise. Numerous Nectin-4 ADCs are in development for treating Nectin-4-positive cancers.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Nectin-4 (Nectin cell adhesion molecule 4) is a type I transmembrane protein.
- Overexpression of Nectin-4 is observed in diverse tumor types.
- This overexpression makes Nectin-4 a significant target for antibody-drug conjugate (ADC) therapies.
Purpose of the Study:
- To review Nectin-4-directed antibody-drug conjugates (ADCs) in clinical and preclinical development.
- To highlight the significance of Nectin-4 as a validated cancer target.
- To discuss the evolving role of Nectin-4 ADCs in cancer therapeutics.
Main Methods:
- Literature review of clinical and preclinical studies.
- Analysis of Nectin-4 expression in various cancers.
- Examination of approved and investigational Nectin-4-directed ADCs.
Main Results:
- The US FDA-approved enfortumab vedotin (EV) validates Nectin-4 as a reliable target antigen.
- Seven Nectin-4-directed ADCs are in clinical trials.
- Eleven Nectin-4-directed ADCs are in preclinical development.
Conclusions:
- Nectin-4 is a clinically validated target for cancer therapy.
- Nectin-4-directed ADCs represent a promising therapeutic strategy.
- The ongoing development of Nectin-4 ADCs offers future treatment options for Nectin-4-positive cancer patients.
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