Reference product (Erbitux); a recombinant chimeric anti-EGFR IgG1 monoclonal antibody that binds EGFR, blocks ligand binding and receptor activation, induces receptor internalization, inhibits downstream signaling (RAS–RAF–MEK–ERK, PI3K–AKT), and mediates ADCC.
Cetuximab is a chimeric IgG1 monoclonal antibody against EGFR (ErbB1/HER1). It binds the extracellular domain of EGFR, blocks ligand (EGF/TGF-alpha) binding, prevents receptor activation and dimerization, promotes receptor internalization, and inhibits downstream RAS-RAF-MEK-ERK and PI3K-AKT signaling, reducing proliferation and survival of EGFR-expressing tumor cells; its IgG1 Fc can also mediate ADCC.
NO
INDIRECT
Cetuximab targets EGFR on tumor cells; its IgG1 Fc engages Fcγ receptors (including CD32A) on immune effector cells to mediate ADCC/ADCP against EGFR-positive cells. CD32A-expressing cells act as effectors, not targets.
Reference product (Erbitux); a recombinant chimeric anti-EGFR IgG1 monoclonal antibody that binds EGFR, blocks ligand binding and receptor activation, induces receptor internalization, inhibits downstream signaling (RAS–RAF–MEK–ERK, PI3K–AKT), and mediates ADCC.
Cetuximab is a chimeric IgG1 monoclonal antibody against EGFR (ErbB1/HER1). It binds the extracellular domain of EGFR, blocks ligand (EGF/TGF-alpha) binding, prevents receptor activation and dimerization, promotes receptor internalization, and inhibits downstream RAS-RAF-MEK-ERK and PI3K-AKT signaling, reducing proliferation and survival of EGFR-expressing tumor cells; its IgG1 Fc can also mediate ADCC.
NO
INDIRECT
Cetuximab’s Fab binds EGFR on tumor cells; its IgG1 Fc engages FcγRI (CD64) on immune effector cells to drive ADCC/ADCP against EGFR+ targets. CD64-expressing cells are not killed by the drug.
HER2-directed antibody–drug conjugate: trastuzumab linked via a cleavable linker to the topoisomerase I inhibitor deruxtecan. Binds HER2, is internalized, releases deruxtecan to induce DNA damage and apoptosis; also blocks HER2 signaling and mediates ADCC, with a bystander effect.
HER2-targeted antibody–drug conjugate: trastuzumab binds HER2 and is internalized; a cleavable linker releases the membrane-permeable topoisomerase I inhibitor deruxtecan (DXd) in tumor cells, inducing DNA damage and apoptosis. The trastuzumab moiety also inhibits HER2 signaling and mediates ADCC, enabling a bystander cytotoxic effect.
YES
DIRECT
The ADC binds HER2, is internalized, and releases the topoisomerase I inhibitor deruxtecan inside the cell, causing DNA damage and apoptosis; Fc-mediated ADCC also contributes, with a membrane-permeable payload enabling bystander killing.
HER2-directed antibody–drug conjugate: trastuzumab linked via a cleavable linker to the topoisomerase I inhibitor deruxtecan. Binds HER2, is internalized, releases deruxtecan to induce DNA damage and apoptosis; also blocks HER2 signaling and mediates ADCC, with a bystander effect.
HER2-targeted antibody–drug conjugate: trastuzumab binds HER2 and is internalized; a cleavable linker releases the membrane-permeable topoisomerase I inhibitor deruxtecan (DXd) in tumor cells, inducing DNA damage and apoptosis. The trastuzumab moiety also inhibits HER2 signaling and mediates ADCC, enabling a bystander cytotoxic effect.
NO
INDIRECT
T-DXd targets HER2, is internalized, and releases deruxtecan that inhibits topoisomerase I to cause DNA damage/apoptosis in HER2+ cells; topoisomerase I expression alone is not selectively targeted (any killing would be via bystander exposure).
Humanized anti-HER2 monoclonal antibody that inhibits HER2 signaling and mediates antibody-dependent cellular cytotoxicity (ADCC).
Humanized IgG1 monoclonal antibody targeting HER2 (ERBB2) that binds the receptor’s extracellular domain, inhibits HER2-driven signaling and proliferation, and recruits immune effector cells to mediate antibody-dependent cellular cytotoxicity (ADCC) against HER2-overexpressing tumor cells.
YES
DIRECT
Trastuzumab binds HER2 on target cells and its Fc engages Fcγ receptor–bearing immune effectors (e.g., NK cells) to trigger antibody-dependent cellular cytotoxicity (ADCC), killing HER2-expressing cells.