HER2-targeted antibody-drug conjugate (T-DXd) that binds HER2, internalizes, and releases a cleavable deruxtecan topoisomerase I inhibitor payload causing DNA damage with a bystander effect.
HER2-targeted antibody–drug conjugate: the trastuzumab antibody binds HER2 on tumor cells, is internalized, and a cleavable linker releases the deruxtecan (DXd) topoisomerase I inhibitor payload, causing DNA damage, cell-cycle arrest, and apoptosis with a bystander effect; additionally can mediate ADCC.
NO
INDIRECT
HER2-directed ADC: trastuzumab binds HER2, is internalized, and releases deruxtecan (a topoisomerase I inhibitor) causing DNA damage and apoptosis with bystander effect and ADCC. Topoisomerase I is only the intracellular enzymatic target of the payload, not the binding target.
TROP2-targeted antibody-drug conjugate (Dato-DXd) that binds TROP2, internalizes, and releases a cleavable deruxtecan topoisomerase I inhibitor payload causing DNA damage with a bystander effect.
TROP2-targeted antibody-drug conjugate that binds TROP2 on tumor cells, internalizes, and releases a cleavable deruxtecan (DXd) topoisomerase I inhibitor payload, stabilizing Topo I–DNA complexes to induce DNA breaks and cytotoxicity with a bystander effect.
YES
DIRECT
ADC binds TROP2 on tumor cells, is internalized, and releases the DXd topoisomerase I inhibitor that induces DNA breaks and apoptosis; also enables a bystander effect.
TROP2-targeted antibody-drug conjugate (Dato-DXd) that binds TROP2, internalizes, and releases a cleavable deruxtecan topoisomerase I inhibitor payload causing DNA damage with a bystander effect.
TROP2-targeted antibody-drug conjugate that binds TROP2 on tumor cells, internalizes, and releases a cleavable deruxtecan (DXd) topoisomerase I inhibitor payload, stabilizing Topo I–DNA complexes to induce DNA breaks and cytotoxicity with a bystander effect.
NO
INDIRECT
Dato-DXd targets TROP2 on tumor cells, is internalized, and releases the DXd payload that inhibits topoisomerase I to cause DNA breaks and apoptosis (with a bystander effect). DNA topoisomerase I is the intracellular enzymatic payload target, not the antigen used to select cells for killing.
Anti-HER2 monoclonal antibody that inhibits HER2 signaling and mediates ADCC.
Humanized IgG1 monoclonal antibody targeting HER2/ERBB2; binds the extracellular domain on HER2-overexpressing tumor cells to block receptor signaling and dimerization, promote receptor downregulation, and engage Fc receptors to mediate antibody-dependent cell-mediated cytotoxicity (ADCC).
YES
DIRECT
After binding HER2, trastuzumab’s Fc engages Fcγ receptors on NK cells and other effectors to mediate ADCC (and some CDC), resulting in killing of HER2-expressing cells.
Autologous or allogeneic T cells transduced with a lentiviral vector to express a CD19-specific chimeric antigen receptor; IV infusion at 2×10^6–1×10^7 CAR-T/kg with dose escalation to define MTD; mediates MHC-independent cytotoxicity against malignant B cells.
Autologous or allogeneic T cells are lentivirally engineered to express a CD19-specific chimeric antigen receptor. Upon CAR binding to CD19 on B-lineage malignant cells, the T cells are activated in an MHC-independent manner, expand, and mediate cytotoxicity via perforin/granzyme release and cytokine signaling, leading to targeted depletion of CD19+ tumor cells.
YES
DIRECT
CAR T cells bind CD19 on target cells, become activated, and kill them via perforin/granzyme-mediated cytolysis (MHC-independent), with additional death signals from cytokines/Fas–FasL.