HER2-directed antibody–drug conjugate (IgG1 trastuzumab linked via a cleavable linker to the deruxtecan [DXd] topoisomerase I inhibitor). Binds HER2, internalizes, releases DXd in lysosomes to inhibit TOP1 causing DNA damage; trastuzumab component can inhibit HER2 signaling and mediate ADCC; payload can exert a bystander effect.
HER2-directed antibody-drug conjugate: trastuzumab (IgG1) linked via a cleavable linker to deruxtecan (DXd), a topoisomerase I inhibitor. After HER2 binding and internalization, lysosomal cleavage releases DXd to inhibit TOP1, causing DNA damage and tumor cell death. The trastuzumab component also blocks HER2 signaling and mediates ADCC; the membrane-permeable payload can produce a bystander effect.
NO
INDIRECT
The ADC targets HER2 (not TOP1) for binding and internalization; once inside HER2+ cells, the released deruxtecan inhibits TOP1, causing DNA damage and apoptosis (with possible ADCC and bystander effects).
TROP2-directed antibody–drug conjugate (IgG1 anti-TROP2 datopotamab linked via a cleavable linker to the deruxtecan [DXd] topoisomerase I inhibitor). Binds TROP2, internalizes, releases DXd in lysosomes to inhibit TOP1 causing DNA damage; membrane-permeable payload may produce a bystander effect.
TROP2-directed IgG1 antibody–drug conjugate that binds TROP2 on tumor cells, is internalized, and releases the DXd (deruxtecan) topoisomerase I inhibitor via a cleavable linker in lysosomes; DXd inhibits TOP1, causing DNA damage and apoptosis, with a membrane-permeable payload enabling a bystander effect.
YES
DIRECT
ADC binds TROP2 on target cells, is internalized, and releases the DXd topoisomerase I inhibitor after lysosomal linker cleavage, causing DNA damage and apoptosis (with a membrane-permeable payload that can also cause a bystander effect).
TROP2-directed antibody–drug conjugate (IgG1 anti-TROP2 datopotamab linked via a cleavable linker to the deruxtecan [DXd] topoisomerase I inhibitor). Binds TROP2, internalizes, releases DXd in lysosomes to inhibit TOP1 causing DNA damage; membrane-permeable payload may produce a bystander effect.
TROP2-directed IgG1 antibody–drug conjugate that binds TROP2 on tumor cells, is internalized, and releases the DXd (deruxtecan) topoisomerase I inhibitor via a cleavable linker in lysosomes; DXd inhibits TOP1, causing DNA damage and apoptosis, with a membrane-permeable payload enabling a bystander effect.
NO
INDIRECT
Killing is determined by TROP2 binding and internalization; the released DXd payload inhibits topoisomerase I to cause DNA damage and apoptosis, with possible bystander effect, but TOP1 expression itself is not the selective target.
Autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy in which a patient’s T cells are engineered to express a CD19-targeted CAR to deplete CD19+ B-lineage cells (including plasmablasts), aiming to reduce pathogenic autoantibody production in autoimmune diseases.
Autologous T cells are engineered to express a CD19-specific chimeric antigen receptor that recognizes CD19 on B-lineage cells (including plasmablasts). Upon antigen engagement, CAR T cells activate and mediate cytotoxic killing of CD19+ cells, depleting pathogenic B-cell populations to reduce autoantibody production and reset humoral immunity in autoimmune disease.
YES
DIRECT
CD19-targeted CAR T cells bind CD19 on B-lineage cells and induce cytolysis via T-cell effector mechanisms (perforin/granzyme-mediated apoptosis, Fas–FasL).
An anti-HER2 antibody–drug conjugate administered IV every 6 weeks (2.2 mg/kg). The monoclonal antibody targets HER2, is internalized, and releases the auristatin-derived microtubule inhibitor Amberstatin-269 to disrupt tubulin polymerization, causing G2/M arrest and apoptosis; the antibody component may also inhibit HER2 signaling and mediate ADCC.
HER2-targeted monoclonal antibody-drug conjugate. After binding HER2 and internalization, it releases an auristatin (MMAF analog) payload that inhibits microtubule polymerization, causing G2/M arrest and apoptosis; the antibody component may also inhibit HER2 signaling and mediate antibody-dependent cellular cytotoxicity (ADCC).
NO
INDIRECT
ARX788 targets HER2 on the cell surface, is internalized, and then releases an auristatin payload that binds beta-tubulin to block microtubule polymerization, causing G2/M arrest and apoptosis; beta-tubulin is not the directly targeted antigen.