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The EGFRxCD33 bispecific antibody is a T cell-engaging bispecific antibody (T-BsAb) developed as a research tool to evaluate the necessity of bivalent tumor binding for therapeutic efficacy in solid tumors. It is constructed using a 2+2 IgG-[L]-scFv format, which incorporates two anti-CD3 single-chain variable fragments (scFvs) attached to the light chains of a heterodimeric IgG. The IgG portion consists of one Fab arm specific for the Epidermal Growth Factor Receptor (EGFR) and one Fab arm specific for CD33, the latter serving as a non-tumor-targeting control in the context of pancreatic ductal adenocarcinoma (PDAC). This 'tumor-monovalent' design results in significantly reduced avidity and T-cell mediated cytotoxicity compared to bivalent counterparts. In preclinical studies, the EGFRxCD33 construct failed to demonstrate therapeutic efficacy against PDAC xenografts, highlighting the importance of bivalent tumor engagement for potent anti-tumor activity.
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