HER2xCD33 bispecific antibody

The HER2xCD33 bispecific antibody is a T cell-engaging bispecific antibody (T-BsAb) designed in a 2+2 IgG-[L]-scFv format. It was developed as a research tool to evaluate the significance of bivalent versus monovalent tumor antigen binding in the treatment of pancreatic ductal adenocarcinoma (PDAC). The construct is a heterodimer featuring one Fab arm specific for Human Epidermal Growth Factor Receptor 2 (HER2) and one Fab arm specific for CD33, which serves as a non-tumor-targeting control in HER2-positive PDAC models. T-cell recruitment is achieved via two anti-CD3 single-chain variable fragments (scFvs) fused to the light chains of the IgG scaffold. Preclinical evaluations demonstrated that this monovalent HER2-binding construct has significantly lower avidity and T-cell mediated cytotoxicity compared to bivalent HER2xHER2 versions and lacks therapeutic efficacy in vivo, underscoring the requirement for bivalent tumor engagement for effective T-cell redirection in solid tumors.

Other names

HER2xCD33 T-BsAbHER-2xCD33 T-BsAbHER 2xCD33 T-BsAbHER2xCD33 heterodimeric BsAbHER-2xCD33 heterodimeric BsAbHER 2xCD33 heterodimeric BsAb