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anti-B7-H3/anti-EGFR bispecific antibody-drug conjugate IBI3001

An antibody-drug conjugate (ADC) composed of a bispecific antibody directed against the tumor associated antigens (TAAs) B7-homologue 3 (B7-H3, CD276) and human epidermal growth factor receptor (EGFR) that is site-specifically glycan-conjugated to the camptothecin analog exatecan, with potential antineoplastic activity. Upon administration, anti-B7-H3/anti-EGFR bispecific ADC IBI3001 targets and simultaneously binds to B7-H3 and EGFR expressed on tumor cells. This blocks EGFR activation by ligands and EGFR-mediated signaling. Upon binding, internalization and linker cleavage, exatecan is released and inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis in B7-H3- and EGFR-expressing tumor cells. In addition, IBI3001 causes a bystander effect, thereby killing both EGFR- and B7-H3-positive cancer cells and EGFR- and B7-H3-negative cancer cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells. It is an immunoregulatory protein and negative regulator of T-cell activation and its overexpression plays a key role in tumor cell invasion and metastasis. B7-H3 and EGFR are co-expressed in multiple solid tumors.
Synonym:anti-B7-H3/anti-EGFR bispecific ADC IBI3001
anti-B7-H3/EGFR ADC IBI3001
bispecific ADC IBI3001
Code name:IBI 3001
IBI-3001
IBI3001
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