Anti-ETB Antibody Development

Aided by advanced technical platform, Creative Biolabs provides customized antibody services to help your projects of monoclonal antibodies (mAbs) preparation. Our professional scientists have extensive experience in antibody production, synthetic chemistry, and bio-conjugation. Nowadays, we are committed to providing high-quality services and products against endothelin receptor B (ETB) to promote the development of human diseases therapeutics.

ETB

Endothelin-1 (ET-1) is a major regulator of vascular function, acting via both endothelin receptor type A (ETA) and type B (ETB). ETB is a G-protein coupled receptor with a molecular mass of approximately 50 KDa. ETB is composed of a long extracellular N-terminus sequence, seven helical transmembrane domains (TMDs), three extracellular and three intracellular loops, and a cytoplasmic C-terminus tail. ETB in the endothelium mediates the release of relaxing factors such as nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor, and could also play a role in ET-1 clearance. ETB is over-expressed in various human cancer compartment, specifically in the tumor endothelium, where its activation by ET-1 suppresses T-cell adhesion and homing to tumors. ETB specific blockade at the tumor endothelium proved to be therapeutically effective for tumor immune therapy by increasing T-cell homing to tumors and enhancing the efficacy of otherwise ineffective.

Fig.1 Human ETB structure. (Mazzuca, 2012)

Antibody-based Therapy

Anti-ETB antibodies could be designed to block cancer-driving signaling pathways. Since expression of ETB is highly restricted in normal adult tissues and is over-expressed in the majority of metastatic melanomas, ETB becomes attractive targets for pharmaco delivery applications and different attempts have been made based on anti-ETB antibodies. For example, DEDN-6256A (RG-7636) is an antibody-drug conjugate (ADC) with the anti-mitotic agent monomethyl auristatin (MMAE) linked to the humanized IgG1 anti-ETB mAb, representing a novel targeted treatment against melanoma. Upon binding to cells, the antibody is rapidly internalized and the released drug disrupts cell proliferation by interfering with microtubule dynamics. In both rodent and primate models, the anti-ETB ADC exhibits favorable pharmacokinetic properties and is well-tolerated at exposures predicted to be efficacious based on tumor xenograft studies. Besides, anti-ETB ADCs can be used in combination with signaling pathway inhibitors with well therapeutic use in the majority of human melanoma cases.

Creative Biolabs is committed to providing high-quality products and chemical synthesis services to promote the progress of antibody development projects. If you are looking for anti-ETB antibody development services, please don’t hesitate to contact us for more information and a detailed quote.

Reference

1. Mazzuca, M. Q.; Khalil, R. A. Vascular endothelin receptor type B: structure, function and dysregulation in vascular disease. Biochemical pharmacology. 2012, 84(2), 147-162.

For Research Use Only. NOT FOR CLINICAL USE.