TROP2-targeted antibody-drug conjugate (aka iza-bren; izalontamab brengitecan; BMS-986507) that delivers the topoisomerase I inhibitor brengitecan to TROP2-expressing tumor cells, causing DNA damage and cell death.
TROP2-targeted monoclonal antibody linked to the topoisomerase I inhibitor brengitecan. After binding TROP2 on tumor cells, the ADC is internalized and releases brengitecan, which inhibits topo I, causing DNA damage (replication-associated strand breaks) and tumor cell death, with potential bystander effect in TROP2-expressing tumors.
YES
DIRECT
The TROP2-binding ADC is internalized and releases the topoisomerase I inhibitor brengitecan inside TROP2-expressing cells, causing replication-associated DNA damage and cell death, with potential bystander killing.
TROP2-targeted antibody-drug conjugate (aka iza-bren; izalontamab brengitecan; BMS-986507) that delivers the topoisomerase I inhibitor brengitecan to TROP2-expressing tumor cells, causing DNA damage and cell death.
TROP2-targeted monoclonal antibody linked to the topoisomerase I inhibitor brengitecan. After binding TROP2 on tumor cells, the ADC is internalized and releases brengitecan, which inhibits topo I, causing DNA damage (replication-associated strand breaks) and tumor cell death, with potential bystander effect in TROP2-expressing tumors.
NO
INDIRECT
The ADC binds a surface antigen (e.g., TROP2), is internalized, and releases brengitecan, which inhibits DNA topoisomerase I to cause DNA damage and kill the antigen-positive cells; topoisomerase I is the intracellular payload target, not the directly targeted cell-surface antigen.
Chimeric IgG1 monoclonal antibody against EGFR (HER1); blocks ligand binding and receptor activation, inhibiting downstream RAS/RAF/MEK/ERK and PI3K/AKT pathways and inducing NK cell–mediated ADCC.
Chimeric IgG1 monoclonal antibody against EGFR (HER1) that binds the receptor’s extracellular domain to block ligand binding and prevent receptor activation and dimerization, thereby inhibiting downstream RAS/RAF/MEK/ERK and PI3K/AKT signaling and tumor cell proliferation; its IgG1 Fc also induces NK cell–mediated ADCC.
YES
DIRECT
Cetuximab binds EGFR on target cells and its IgG1 Fc engages NK cells (via FcγRIIIa) to mediate ADCC; it can also activate complement (CDC). EGFR blockade itself is antiproliferative.
An antibody–drug conjugate (Dato‑DXd; DS‑1062a) comprising a humanized IgG1 antibody targeting TROP2 linked via a cleavable linker to the cytotoxic payload DXd (a topoisomerase I inhibitor). After binding TROP2 and internalization, DXd is released to induce DNA damage, S‑phase arrest, apoptosis, and a bystander effect.
Humanized IgG1 antibody targeting TROP2 linked via a cleavable linker to DXd (an exatecan-derived topoisomerase I inhibitor). After TROP2 binding and internalization, lysosomal cleavage releases DXd, which stabilizes the topoisomerase I–DNA complex, causing DNA strand breaks, S-phase arrest, apoptosis, and a bystander cytotoxic effect.
YES
DIRECT
ADC binds TROP2 on target cells, is internalized, and lysosomal cleavage releases the DXd topoisomerase I inhibitor, causing DNA damage (topo I–DNA complex stabilization), S‑phase arrest, and apoptosis; with a potential bystander effect.
An antibody–drug conjugate (Dato‑DXd; DS‑1062a) comprising a humanized IgG1 antibody targeting TROP2 linked via a cleavable linker to the cytotoxic payload DXd (a topoisomerase I inhibitor). After binding TROP2 and internalization, DXd is released to induce DNA damage, S‑phase arrest, apoptosis, and a bystander effect.
Humanized IgG1 antibody targeting TROP2 linked via a cleavable linker to DXd (an exatecan-derived topoisomerase I inhibitor). After TROP2 binding and internalization, lysosomal cleavage releases DXd, which stabilizes the topoisomerase I–DNA complex, causing DNA strand breaks, S-phase arrest, apoptosis, and a bystander cytotoxic effect.
YES
INDIRECT
After the ADC binds TROP2 and is internalized, the DXd payload is released and inhibits DNA topoisomerase I, causing DNA breaks, S-phase arrest, and apoptosis; payload can also diffuse to nearby cells (bystander killing).