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EGFRxHER2 bispecific antibody
- Development stage
- Preclinical
- Lead developer
- Memorial Sloan Kettering Cancer Center
- Modality
- Bispecific Antibodies → Multispecific Antibodies → Engineered Antibody Formats → Antibody-Based Therapeutics, T-cell Engagers → Multispecific Antibodies → Engineered Antibody Formats → Antibody-Based Therapeutics
- Administration
- Intravenous
01
Overview
EGFRxHER2 bispecific antibody is a heterodimeric T cell-engaging bispecific antibody (T-BsAb) designed for the treatment of pancreatic ductal adenocarcinoma (PDAC). Developed using a specialized 2+2 IgG-[L]-scFv format, the molecule features two anti-CD3 single-chain variable fragments (scFvs) attached to the light chains of an IgG scaffold to recruit and activate polyclonal T cells. The tumor-targeting component consists of one Fab arm specific for the epidermal growth factor receptor (EGFR), derived from cetuximab, and one Fab arm specific for human epidermal growth factor receptor 2 (HER2), derived from trastuzumab. This heterodimeric configuration is achieved through a 'knob-into-hole' Fab arm exchange strategy. The antibody is designed to selectively target tumor cells expressing both EGFR and HER2, potentially increasing therapeutic index by sparing normal tissues that express only one of the targets, thereby reducing 'on-target/off-tumor' toxicities.
- Other names
- EGFRxHER2 T-BsAbEGFRxHER-2 T-BsAbEGFRxHER 2 T-BsAbEGFRxHER2 heterodimeric BsAbEGFRxHER-2 heterodimeric BsAbEGFRxHER 2 heterodimeric BsAbEGFRxHER2 2+2 IgG-[L]-scFv
02
Targets
EGFR T790M (Epidermal growth factor receptor T790M mutant)ERBB2 (Erb-b2 receptor tyrosine kinase 2)
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