Autologous gene-modified CAR T-cell therapy for relapsed/refractory multiple myeloma; patient T cells are engineered to express a CAR that recognizes myeloma-associated antigens and, upon binding, activates T-cell cytotoxicity.
Autologous patient T cells are gene-modified to express a chimeric antigen receptor that recognizes myeloma-associated surface antigens; upon antigen binding, CAR signaling activates and expands the T cells, inducing cytokine release and targeted cytotoxic killing of malignant plasma cells.
YES
DIRECT
CAR T cells recognize the myeloma-associated surface antigen via the CAR, activate, and directly kill antigen-expressing cells through perforin/granzyme-mediated cytotoxicity (and Fas–FasL apoptosis).
Cord blood–derived natural killer (NK) cells genetically engineered to express a CD19-directed chimeric antigen receptor for antigen-specific recognition and cytotoxic killing of CD19-positive B cells in B-cell malignancies.
Cord blood–derived NK cells are engineered to express a CD19-specific chimeric antigen receptor, enabling antigen-dependent recognition and cytotoxic killing of CD19-positive B cells in B-cell malignancies. In this construct, IL-15 supports NK activation, proliferation, and persistence, while IL-10 modulates inflammatory responses to enhance antitumor activity and potentially reduce toxicity.
NO
INDIRECT
Anti-CD19 CAR-NK cells recognize CD19 and kill CD19+ B cells via CAR-triggered NK effector mechanisms (perforin/granzymes). IL-15Rα is not targeted; IL-15/IL-15Rα signaling only supports NK activation/persistence.
HER2-targeted antibody–drug conjugate of trastuzumab linked to the maytansinoid DM1 microtubule inhibitor; delivers cytotoxic payload to HER2-overexpressing cells while retaining trastuzumab activity.
Ado-trastuzumab emtansine (T-DM1) is a HER2-targeted antibody–drug conjugate in which trastuzumab is linked to the microtubule inhibitor DM1. It binds HER2 on tumor cells, is internalized, and releases DM1 to disrupt microtubules and induce cell death, while trastuzumab concurrently inhibits HER2 signaling and mediates ADCC.
NO
INDIRECT
T-DM1 targets HER2 on the cell surface, is internalized, and releases DM1 that binds beta-tubulin to disrupt microtubules and cause cell death. Tubulin expression alone does not make cells susceptible; HER2-mediated uptake is required.
HER2-targeted antibody–drug conjugate of trastuzumab linked to a topoisomerase I inhibitor (deruxtecan) via a cleavable linker; exhibits high drug-to-antibody ratio and a bystander killing effect.
HER2-targeted antibody–drug conjugate composed of trastuzumab linked via a cleavable linker to deruxtecan (DXd), a membrane-permeable topoisomerase I inhibitor. Binding to HER2 drives internalization and lysosomal cleavage to release DXd, causing DNA damage (single-strand breaks) and apoptosis. The trastuzumab component also inhibits HER2 signaling and can mediate ADCC. High drug-to-antibody ratio and diffusible payload enable a bystander killing effect of neighboring HER2-low tumor cells.
YES
DIRECT
ADC binds HER2, is internalized, and releases the DXd topoisomerase I inhibitor after lysosomal cleavage, causing DNA damage and apoptosis; Fc can also trigger ADCC. Bystander killing may occur via diffusible payload.
HER2-targeted antibody–drug conjugate of trastuzumab linked to a topoisomerase I inhibitor (deruxtecan) via a cleavable linker; exhibits high drug-to-antibody ratio and a bystander killing effect.
HER2-targeted antibody–drug conjugate composed of trastuzumab linked via a cleavable linker to deruxtecan (DXd), a membrane-permeable topoisomerase I inhibitor. Binding to HER2 drives internalization and lysosomal cleavage to release DXd, causing DNA damage (single-strand breaks) and apoptosis. The trastuzumab component also inhibits HER2 signaling and can mediate ADCC. High drug-to-antibody ratio and diffusible payload enable a bystander killing effect of neighboring HER2-low tumor cells.
NO
INDIRECT
T-DXd binds HER2 (not topoisomerase I), is internalized, and releases deruxtecan that inhibits topoisomerase I to cause DNA damage and apoptosis; any killing of topoisomerase I–expressing cells occurs only if they receive the payload (e.g., bystander effect), not because they express topoisomerase I.