ADC Development Services Targeting Nectin 4

Creative Biolabs is a global leader in providing service focus on ADCs development for global pharmaceutical companies and research institutions. Our world-class facilities are backed by a highly experienced team to offer integrated services from antibody discovery to drug conjugation to ADCs characterization. We strive to offer tailored solutions for your ADCs development.

Introduction of Nectin 4

Nectin-4, also known as PVRL4 (poliovirus-receptor-like 4), is a member of the nectin family that involved in the Ca²⁺-independent cellular adhesion. Nectin-4 consists of three extra cellular immunoglobulin domains, a single transmembrane helix and an intracellular domain. Nectin-4 is normally expressed in the embryo and placenta and it is also highly expressed on some cancer cells, including lung, ovarian, and breast cancer in human. During the cancer progress, Nectin-4 plays a role in the tumor cell growth and proliferation through the Rac1-signaling pathway in human lung adenocarcinoma. Besides, Nectin-4 can function in facilitating the attachment of individual cells to each other on a juxtaposed cell, and maintains the transformed properties of breast cancer cells. Thus, Nectin-4 is considered as a biomarker in the cancer diagnosis and therapy.

Ribbon representations of human nectin homodimers showing the overall structural organizations and interfacial residues at the dimer interfaces. Fig.1 Ribbon representations of human nectin homodimers showing the overall structural organizations and interfacial residues at the dimer interfaces. (Samanta, 2015)

Anti-Nectin 4 ADC in Solid Tumors

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. Enfortumab vedotin (also known as ASG‑22ME) is an ADC against the Nectin 4, which is composed of a human anti-nectin-4 antibody linked to the highly potent microtubule-disrupting agent MMAE through a cleavable valine-citrulline linker. Preclinical data showed that Enfortumab vedotin can bind to cell surface-expressed nectin-4 with high affinity and induce cell death in vitro in a dose-dependent manner. Besides, trial results demonstrated that this ADC has potent antitumor activity in the xenograft models of human breast, bladder, pancreatic, and lung cancers. To date, Enfortumab vedotin is assessed in the clinical phase I for the treatment of solid and urothelial tumors. All positive results indicated that Enfortumab vedotin against the nectin-4 is an attractive and promising therapeutic option for multiple solid tumors.

Mechanism of action of enfortumab vedotin. Fig.2 Mechanism of action of enfortumab vedotin.

What Can We Do for You?

Creative Biolabs has extensive experience in the conjugating antibodies to a range of drugs or linker-payloads. At Creative Biolabs, conjugation can be achieved using a wide variety of linkages, exploiting cysteine or lysine residues in the target antibody. The specific antibody is manufactured to a high purity and excess drug and linker are removed post-conjugation using optimal strategy to produce a clean product. Characterization of the final ADC products can be completed using high resolution mass spectrometry techniques or other methods. Our ADCs services include ADC Antibody Screening, DrugLnk™ Custom Synthesis, Antibody Design and Conjugation, ADC in vitro Analysis and ADC in vivo Analysis. For more information of ADC development, please contact us.

Reference

  1. Samanta, D.; Almo, S. C. Nectin family of cell-adhesion molecules: structural and molecular aspects of function and specificity. Cellular and molecular life sciences. 2015, 72(4): 645-658.

For lab research use only, not for any in vivo human use.


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