Engineered Human Antibody with Improved Endothelin Receptor Type A Binding Affinity, Developability, and Serum Persistence Exhibits Excellent Antitumor Potency

Endothelin receptor A (ET A ), a class A G protein-coupled receptor (GPCR), is a promising tumor-associated antigen due to its close association with the progression and metastasis of many types of cancer, such as colorectal, breast, lung, ovarian, and prostate cancer. However, only small-molecule drugs have been developed as ET A antagonists with anticancer effects. In a previous study, we identified an antibody (AG8) with highly selective binding to human ET A through screening of a human naïve immune antibody library. Although both in vitro and in vivo experiments indicated that the identified AG8 had anticancer effects, there is a need for improvement in biochemical and physicochemical properties such as the ET A binding affinity, thermostability, and productivity. In this study, we engineered the framework regions of AG8 and isolated an anti-ET A antibody (MJF1) exhibiting significa…