ADC Development Services Targeting P-Cadherin

Despite P-Cadherin is a classical adhesion molecule with regulatory functions in the normal context. There is a significant association between the overexpression of this molecule and poor prognosis in several carcinomas. As a professional service provider in antibody-drug conjugates (ADC) production for years, Creative Biolabs has successfully completed a significant number of ADC development projects. Our customers, ranging from research institution to large biotech companies, have taken full advantage of our ADC and bioconjugation capabilities. Besides existing Anti-P-Cadherin ADC, Creative Biolabs also offers a comprehensive set of anti-P-Cadherin ADC developments services for our worldwide customers.

Introduction of P-Cadherin

P-Cadherin, also known as Cadherin-3, is a classical calcium dependent cell-cell adhesion glycoprotein. The mature P-Cadherin glycoprotein has a molecular weight (MW) of 118 kDa and it mainly promotes homotypic interactions. It is comprised of three distinct domains, namely extracellular domain, transmembrane domain and cytoplasmic domain. The amino-terminal domain is essential for the creation of lateral dimmers that act together in a zipper-like structure between neighboring cells. Because of the importance of cadherins in cell recognition, adhesion, sorting and signaling, their disruptive function of P-Cadherin has significant implications in disease states, including cancer. Studies showed that P-Cadherin contributes to the survival of aggressive cancer cells. Besides, P-Cadherin is essential for the adhesion of cancer cells to extracellular matrix substrates that are critical for metastatic dissemination, namely laminin, vitronectin and fibronectin. Thus, targeting P-Cadherin in cancer may be a good therapeutic approach, since normal tissues usually express very low levels of this cadherin.

Fig.1 Schematic representation of the structural components of the P-Cadherin adhesive junction. (Albergaria, 2011)

Anti-P-Cadherin ADC in Breast Cancer, Head and Neck Cancer, Oesophageal Cancer

P-Cadherin is frequently over-expressed in high-grade invasive breast carcinomas and has been reported to be an enhancer of migration and invasion of breast cancer cells, being correlated with tumor aggressiveness. Additionally, expression of P-Cadherin is well established as an indicator of poor prognosis in human breast cancer. PCA062 is an anti-P-Cadherin ADC in which an IgG1 monoclonal antibody (mAb) is conjugated to the maytansinoid DM1 via a non-cleavable thioether (SMCC) linker. PCA062 was shown to rapidly internalize and localize to lysosomes following binding to P-Cadherin expressing cells, resulting in antigen-specific cytotoxicity. The PCA062 ADC demonstrated activity in breast, head and neck and bladder carcinoma xenograft models. PCA062 is currently being evaluated in a Phase I trial.

Fig.2 Structures of Trastuzumab emtansine and PCA-062. (Trail, 2018)

Oesophageal carcinoma is known for its extremely aggressive clinical behaviour and, despite improvement in surgical intervention and preoperative management, the overall prognosis for patients is poor. Recently, there has been a growing interest in investigating various molecular markers in oesophageal carcinoma as potential prognostic, diagnostic, and perhaps therapeutic tools. P-Cadherin expression has been investigated intensively in oesophageal carcinomas. The mentioned PCA062 ADC has also been studied in oesophageal cancer with promising result.

What Can We Do for You?

Staffed with a dedicated team of experts, Creative Biolabs is at the forefront of perfect ADC preparation and can support you in conceptualizing and delivering the best linker and conjugation strategy. Our ADC suite is directly supported by our in-house library of payloads and advanced linker-payload synthetic chemistry platforms, providing an end-to-end solution in order to rapidly progress your ADC drug project. Creative Biolabs offers a whole suite of platforms or services needed for ADCs development, which include but not limited to:

• ADC Antibody Screening
• Antibody Design and Conjugation
• DrugLnk™ Custom Synthesis
• ADC in vitro Analysis
• ADC in vivo Analysis

It's exciting to have the opportunity to apply our knowledge of chemistry and biotechnology to boost our customer’s ADC development projects. If you are looking for anti-P-Cadherin ADC development services, Creative Biolabs will be your best choice. Please feel free to contact us for more information.

References

1. Albergaria, A.;et al. P-cadherin role in normal breast development and cancer. International Journal of Developmental Biology. 2011, 55(7-8-9): 811-822.
2. Trail, P. A.; et al. Antibody drug conjugates for treatment of breast cancer: novel targets and diverse approaches in ADC design. Pharmacology & therapeutics. 2018, 181: 126-142.

For Research Use Only. NOT FOR CLINICAL USE.