EGFR and B7-H3 (CD276), dual

Class

Bispecific antibody-drug conjugate (anti-EGFR/anti-B7-H3, topoisomerase I inhibitor payload)

Pathway

Dual tumor-antigen targeting with DNA topoisomerase I inhibition upon internalization

This mechanism describes a bispecific antibody-drug conjugate (ADC) that carries two distinct antibody arms, one recognizing the epidermal growth factor receptor (EGFR) and the other recognizing B7-H3 (CD276), an immune-regulatory surface protein frequently overexpressed on solid tumors. EGFR is a growth-signaling receptor found on many epithelial cancers, while B7-H3 helps tumors evade immune attack and is broadly expressed across tumor types with comparatively limited expression on normal tissue. By engaging both antigens, the conjugate is designed to bind tumor cells more selectively than an antibody targeting either protein alone, since dual recognition can increase avidity for cells expressing both markers while reducing unwanted binding to normal tissue that expresses only one. Once bound, the antibody complex is internalized by the cell, releasing a cytotoxic payload that inhibits topoisomerase I, an enzyme required for resolving DNA strand tension during replication. Blocking this enzyme causes DNA damage that triggers cell death, particularly in rapidly dividing tumor cells. This dual-antigen, payload-delivery approach is relevant across cancers where EGFR and B7-H3 are co-expressed, including several epithelial tumor types, and reflects a broader strategy of using tumor-associated surface proteins as delivery vehicles for potent cytotoxic chemistry.