Nectin-4: ADC Target Protein for Cancer Research

Jul 13, 2023

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).

Mechanism of Enfortumab Vedotin. Image Source: www.seagen.com

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.

BetaLifeScience provides Nectin-4 target proteins to meet the needs of different stages, such as Nectin-4-targeted drug development, functional evaluation, and quality control.

Sample Product Data

(Activity) Validated by ELISA

Immobilized Anti-Human Nectin-4 mAb-mFc at 2μg/ml (100 μl/well) can bind Human Nectin-4-His (Cat#BL-2502NP).The ED50 of Human Nectin-4-His (Cat#BL-2502NP) is 16.29 ng/ml. (Regularly tested)

Immobilized Anti-Human Nectin-4 mAb-mFc at 2μg/ml (100 μl/well) can bind Human Nectin-4-Fc (Cat#BL-2527NP). The ED50 of Human Nectin-4-Fc (Cat#BL-2527NP) is 2.79 ng/ml. (Regularly tested)

Immobilized Human Nectin-4-His-Avi(Cat#BL-0291NP) at 2μg/ml (100 μl/well) can bind Anti-Human Nectin-4 mAb-mFc. The ED50 of Anti-Human Nectin-4 mAb-mFc is 12.28 ng/ml. (Regularly tested)

(Activity) Validated by BLI

Loaded Anti-Human Nectin-4 mAb-mFc on AMQ Biosensor, can bind Human Nectin-4-His(Cat#BL-2502NP) with an affinity constant of 0.60 nM as determined in BLI assay. (Regularly tested)

Loaded Anti-Human Nectin-4 mAb-mFc on AMQ Biosensor, can bind Human Nectin-4-Fc(Cat#BL-2527NP) with an affinity constant of 0.86 nM as determined in BLI assay. (Regularly tested)

Loaded Biotinylated Human Nectin-4-His-Avi(Cat#BL-0291NP) on SA Biosensor, can bind Anti-Human Nectin-4 mAb-mFc with an affinity constant of 1 <10-3 nM as determined in BLI assay. (Regularly tested)

Recommended Nectin-4

Cat. No.	Product Name
BL-2502NP	Recombinant Human Nectin-4 (C-6His)
BL-2527NP	Recombinant Human Nectin-4 (C-Fc)
BL-2326NP	Recombinant Human Nectin-4 (C-mFc)
BL-0291NP	Biotinylated Human Nectin-4 (C-6His-Avi)
BL-2696NP	Recombinant Mouse Nectin-4 (C-6His)
BL-2658NP	Recombinant Mouse Nectin-4 (C-Fc)
BL-2216NP	Recombinant Cynomolgus Nectin-4 (C-6His)
BL-2235NP	Recombinant Cynomolgus Nectin-4 (C-Fc)

References

[1] https://www.seagen.com/
[2] 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

Back to Products and Applications