An Emerging Aim: ADC Target Protein - Nectin-4
The biologics license application (BLA) has been accepted for Enfortumab Vedotin for the treatment of locally advanced or metastatic urothelial carcinoma in patients who have previously received PD-1/PD-L1 inhibitors and platinum-containing chemotherapy. Enfortumab Vedotin is the first domestically submitted targeted antibody-drug conjugate that specifically targets Nectin-4.
Enfortumab vedotin-ejfv (PADCEV®) is a first-in-class antibody-drug conjugate (ADC) that targets Nectin-4, a cell surface protein highly expressed in bladder cancer. Preclinical data suggest that the anticancer activity of Enfortumab Vedotin is attributed to its binding to cells expressing Nectin-4, followed by internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell. This is believed to inhibit cell proliferation (cell cycle arrest) and induce programmed cell death (apoptosis).
Nectin-4, also known as Poliovirus Receptor-Like 4 (PVRL4), is a type I transmembrane protein and a member of the Nectin-like cell adhesion molecule family. Nectin-4 is highly expressed in normal embryonic and fetal tissues, but its levels decrease in adulthood, and its distribution in healthy tissues is limited. However, abnormal expression of Nectin-4 has been observed in several common cancer types, including bladder cancer, breast cancer, lung cancer, pancreatic cancer, and ovarian cancer. In the PI3K-AKT signaling pathway, Nectin-4 promotes cancer cell proliferation and metastasis by activating WNT-β-catenin and Rac small G proteins. Nectin-4 also interacts with the tyrosine kinase receptor ERBB2, promoting its activation and stimulating the PI3K-AKT signaling pathway. Therefore, Nectin-4 has emerged as an important target for the treatment of various solid tumors[1].
Currently, Enfortumab Vedotin is the only ADC (Antibody-Drug Conjugate) targeting Nectin-4 that is approved and marketed worldwide. There are only 10 global pharmaceutical companies conducting research on Nectin-4-targeting drugs.
Beta LifeScience provides Nectin-4 target proteins to meet the needs of different stages, such as Nectin-4-targeted drug development, functional evaluation, and quality control.
Recommended Nectin-4
Recombinant Human Nectin-4 (C-6His)
Recombinant Human Nectin-4 (C-Fc)
Recombinant Human Nectin-4 (C-mFc)
Biotinylated Human Nectin-4 (C-6His-Avi)
Recombinant Mouse Nectin-4 (C-6His)
Recombinant Mouse Nectin-4 (C-Fc)
Recombinant Cynomolgus Nectin-4 (C-6His)
Recombinant Cynomolgus Nectin-4 (C-Fc)
References
[1] Heath, Elisabeth I, and Jonathan E Rosenberg. “The biology and rationale of targeting nectin-4 in urothelial carcinoma.” Nature reviews. Urology vol. 18,2 (2021): 93-103. doi:10.1038/s41585-020-00394-5