Anti-HER2 antibody–drug conjugate delivering a topoisomerase I inhibitor payload to induce DNA damage.
Anti-HER2 antibody–drug conjugate (trastuzumab linked to the topoisomerase I inhibitor deruxtecan). After HER2 binding and internalization, deruxtecan is released to inhibit topoisomerase I, inducing DNA damage, replication arrest, and apoptosis; also elicits ADCC and a bystander killing effect.
NO
INDIRECT
The ADC targets HER2, is internalized, and releases deruxtecan that inhibits Topoisomerase I within HER2+ cells, causing DNA damage and apoptosis; ADCC and bystander effects can also contribute.
Anti-HER2 monoclonal antibody (trastuzumab) conjugated to the microtubule inhibitor DM1 via a nonreducible linker. The antibody binds HER2 on tumor cells and is internalized; intracellular DM1 binds tubulin, disrupting microtubule dynamics to cause mitotic arrest and cell death. The trastuzumab component also inhibits HER2 signaling and can mediate ADCC.
YES
DIRECT
An ADC: trastuzumab binds HER2 and is internalized; lysosomal processing releases DM1, which binds tubulin to disrupt microtubules, causing mitotic arrest and apoptosis. The antibody can also mediate ADCC.
Anti-HER2 monoclonal antibody (trastuzumab) conjugated to the microtubule inhibitor DM1 via a nonreducible linker. The antibody binds HER2 on tumor cells and is internalized; intracellular DM1 binds tubulin, disrupting microtubule dynamics to cause mitotic arrest and cell death. The trastuzumab component also inhibits HER2 signaling and can mediate ADCC.
NO
INDIRECT
T-DM1 targets HER2 on the cell surface; after HER2-mediated internalization, the DM1 payload binds beta‑tubulin to disrupt microtubules and cause mitotic arrest/apoptosis. Tubulin expression alone does not make cells susceptible—HER2 expression is required for delivery.
Anti-HER2 monoclonal antibody that blocks HER2 signaling and mediates antibody-dependent cellular cytotoxicity (ADCC).
Humanized anti-HER2 (ERBB2) monoclonal antibody that binds the extracellular domain (domain IV) of HER2, suppressing HER2-driven signaling (e.g., PI3K/AKT/MAPK) and engaging Fcγ receptors to induce antibody-dependent cellular cytotoxicity (ADCC) against HER2-overexpressing tumor cells.
YES
DIRECT
Trastuzumab binds HER2 on tumor cells and recruits Fc gamma receptor-bearing immune cells to mediate ADCC (and some CDC), killing HER2+ cells; HER2 signaling blockade can also promote apoptosis.
Anti-CLDN18.2 antibody-drug conjugate that binds claudin 18.2 on tumor cells, is internalized, and delivers a cytotoxic payload to kill CLDN18.2-expressing cells.
Anti-CLDN18.2 monoclonal antibody linked to MMAE; binds CLDN18.2 on tumor cells, is internalized, and releases MMAE to inhibit tubulin polymerization, causing G2/M arrest and apoptosis in CLDN18.2-expressing cells.
YES
DIRECT
The ADC binds CLDN18.2 on tumor cells, is internalized, and releases MMAE, which inhibits tubulin polymerization leading to G2/M arrest and apoptosis of the target-expressing cells.