HER2-directed antibody-drug conjugate (T-DXd; DS-8201a, ENHERTU) consisting of the humanized IgG1 monoclonal antibody trastuzumab linked via a cleavable tetrapeptide linker to DXd, a membrane-permeable exatecan derivative and topoisomerase I inhibitor; administered IV 5.4 mg/kg every 3 weeks. Binds HER2, is internalized, and releases DXd in lysosomes to inhibit topoisomerase I, causing DNA damage and apoptosis with a bystander effect; also inhibits HER2 signaling and mediates ADCC.
Humanized anti-HER2 IgG1 (trastuzumab) linked via a cleavable tetrapeptide to DXd, a membrane-permeable exatecan derivative and topoisomerase I inhibitor. After binding HER2 and internalization, the linker is cleaved in lysosomes to release DXd, which inhibits Top1, leading to DNA damage, replication arrest, and apoptosis with a bystander effect; the antibody also inhibits HER2 signaling and mediates ADCC.
YES
DIRECT
HER2-binding ADC is internalized; lysosomal cleavage releases the topoisomerase I inhibitor DXd, causing DNA damage and apoptosis; Fc also mediates ADCC and there is a bystander killing effect.
HER2-directed antibody-drug conjugate (T-DXd; DS-8201a, ENHERTU) consisting of the humanized IgG1 monoclonal antibody trastuzumab linked via a cleavable tetrapeptide linker to DXd, a membrane-permeable exatecan derivative and topoisomerase I inhibitor; administered IV 5.4 mg/kg every 3 weeks. Binds HER2, is internalized, and releases DXd in lysosomes to inhibit topoisomerase I, causing DNA damage and apoptosis with a bystander effect; also inhibits HER2 signaling and mediates ADCC.
Humanized anti-HER2 IgG1 (trastuzumab) linked via a cleavable tetrapeptide to DXd, a membrane-permeable exatecan derivative and topoisomerase I inhibitor. After binding HER2 and internalization, the linker is cleaved in lysosomes to release DXd, which inhibits Top1, leading to DNA damage, replication arrest, and apoptosis with a bystander effect; the antibody also inhibits HER2 signaling and mediates ADCC.
NO
INDIRECT
Trastuzumab deruxtecan binds HER2, is internalized, and releases DXd that inhibits topoisomerase I, causing DNA damage and apoptosis (with bystander effect). Topoisomerase I expression alone does not target cells for killing.
HER2-directed antibody-drug conjugate (T-DXd; DS-8201a, ENHERTU) consisting of the humanized IgG1 monoclonal antibody trastuzumab linked via a cleavable tetrapeptide linker to DXd, a membrane-permeable exatecan derivative and topoisomerase I inhibitor; administered IV 5.4 mg/kg every 3 weeks. Binds HER2, is internalized, and releases DXd in lysosomes to inhibit topoisomerase I, causing DNA damage and apoptosis with a bystander effect; also inhibits HER2 signaling and mediates ADCC.
Humanized anti-HER2 IgG1 (trastuzumab) linked via a cleavable tetrapeptide to DXd, a membrane-permeable exatecan derivative and topoisomerase I inhibitor. After binding HER2 and internalization, the linker is cleaved in lysosomes to release DXd, which inhibits Top1, leading to DNA damage, replication arrest, and apoptosis with a bystander effect; the antibody also inhibits HER2 signaling and mediates ADCC.
NO
INDIRECT
The ADC binds HER2 on tumor cells, is internalized, and releases a topoisomerase I–inhibiting payload; its Fc engages CD16a on NK cells to mediate ADCC against HER2+ cells. CD16a-expressing cells are not targeted for killing.
Bispecific T-cell engager (BiTE) that links CD3 on T cells to CD19 on B-ALL cells to drive T-cell cytotoxicity.
Bispecific T-cell engager (BiTE) antibody that simultaneously binds CD3 on T cells and CD19 on B cells, bringing them into proximity to trigger TCR/CD3 signaling and T-cell–mediated cytotoxicity (perforin/granzyme) against CD19-positive B-lymphoblasts.
YES
DIRECT
Blinatumomab links CD19 on target B cells to CD3 on T cells, activating T cells to form a cytolytic synapse and kill CD19+ cells via perforin/granzyme-mediated apoptosis.
Bispecific T-cell engager (BiTE) that links CD3 on T cells to CD19 on B-ALL cells to drive T-cell cytotoxicity.
Bispecific T-cell engager (BiTE) antibody that simultaneously binds CD3 on T cells and CD19 on B cells, bringing them into proximity to trigger TCR/CD3 signaling and T-cell–mediated cytotoxicity (perforin/granzyme) against CD19-positive B-lymphoblasts.
NO
INDIRECT
Blinatumomab engages CD3ε on T cells and CD19 on B cells to activate T cells, which then kill CD19+ targets via perforin/granzyme; CD3ε-expressing T cells are not the cells killed.