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Nectin-4 is reported to be overexpressed in metastatic solid tumors, and it has been used in the ADCs development for cancer therapy as a potential target. BOC Sciences released a complete set of ADC drug development services for CD19, CD22, EGFR, and other tumor targets, dedicated to helping pharmaceutical partners drive forward the development of innovative cancer treatments.
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Nectin-4, also known as poliovirus receptor-related protein 4 (PVRL4), is a transmembrane protein belonging to the nectin family of immunoglobulin-like molecules. This family consists of four members (nectin-1 to -4), which play important physiologic roles in multiple homeostatic and developmental processes through their involvement in cellular adhesion, differentiation, proliferation, migration, and immunemodulatory signaling. Multiple studies have provided evidences that Nectin-4 is linked with carcinogenesis and disease severity of a cancer patient. Nectin-4 has been established as a novel biomarker for the worst prognosis in cancer and associated with different facets of tumor including proliferation, angiogenesis, metastasis, tumor relapse, DNA repair etc. Additionally, Nectin-4 has been found to be highly expressed in several malignancies, such as bladder, breast, lung, pancreatic, ovarian, head & neck, and esophageal, supporting the rationale for its use as a target antigen for ADCs.
Fig. 1. Schematic representation of the three-domain structures of (a) the Nectin family of proteins and (b) Nectin-4 (European Journal of Pharmacology. 2021, 911: 174516).
Development of ADCs for the treatment of urothelial carcinoma is led by enfortumab vedotin (EV), which consists of a fully human monoclonal antibody targeting Nectin-4 that binds to a microtubule inhibitor MMAE via a cleavable linker. DAR analysis indicated that approximately 3.8 MMAE molecules are conjugated through cysteines via the same cleavable linker technology. Mechanistically, binding of EV to the Ig-like loops (IgV and IgC loops) of Nectin-4 leads to the stimulation of complex internalization and lysosome mediated cleavage of valine-citrulline linker. Therefore, MMAE is released in target cells to bind to microtubules and enhance microtubule breakdown, ultimately playing a major role in anticancer.
BOC Sciences released a complete set of ADC drug development services for various targets to help pharmaceutical partners drive forward the development of innovative cancer treatments. With expertise and dedication, BOC Sciences will be your best companion in creating customized ADCs or linker-payload complexes to bring your drug development project into the next bright level. If you are interested in our ADC-related services for Nectin-4 targets, such as ADC development for bladder cancer, lung cancer, breast cancer, pancreatic cancer and others, please click here for more information.
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