The functionality of a therapeutic antibody candidate restored by a single mutation from proline to threonine in the variable region.

ABSTRACT: mAbs play an essential role in the therapeutic arsenal. Our laboratory has patented the Rendomab-B49 mAb targeting the endothelin B receptor (ET_B). This G protein-coupled receptor plays a driving role in the progression of numerous cancers. We chimerized our mAb (xiRB49) to evaluate its preclinical therapeutic efficacy in different ET_B⁺ tumor models with an antibody drug conjugate approach. As previously reported, the chimerization process of an antibody can alter its functionality. In this article, we present the chimerization of RB49. xiRB49 purified by Protein A remained perfectly soluble and did not aggregate, but it lost all its ability to recognize ET_B. A detailed analysis of its variable region using IMGT tools allowed us to identify an un

SUBMITTER: Hautiere M 

PROVIDER: S-EPMC10760395 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature