Natural killer cells genetically engineered to express a chimeric antigen receptor to enhance antigen-specific cytotoxicity; given as a single IV infusion (~1–2×10^6 cells/kg) following lymphodepleting chemotherapy. Mechanism: CAR-mediated target recognition combined with innate NK cytotoxic pathways (perforin/granzyme, Fas/TRAIL).
NK cells are genetically engineered to express a chimeric antigen receptor that enables antigen-specific, MHC-independent recognition of tumor cells. CAR engagement activates NK signaling and enhances innate NK cytotoxic mechanisms, leading to target-cell killing via perforin/granzyme release and death-receptor pathways (Fas/TRAIL), along with cytokine secretion to eliminate antigen-expressing tumor cells.
Activated CAR-NK cells express TRAIL that binds DR5 (TRAIL-R2) on target cells, triggering death-receptor (extrinsic) apoptosis via caspase-8; NK cells may also kill via perforin/granzyme.
T-DXd; a HER2-directed antibody-drug conjugate that delivers a topoisomerase I inhibitor (DXd), enabling targeted cytotoxicity and bystander killing, with Fc-mediated immune engagement.
HER2-targeted antibody-drug conjugate: trastuzumab binds HER2, is internalized, and releases the DXd topoisomerase I inhibitor to cause DNA damage, replication arrest, and apoptosis; also engages Fc-mediated ADCC/ADCP and produces a bystander killing effect.
Trastuzumab binds HER2, the ADC is internalized and releases the DXd topoisomerase I inhibitor, causing DNA damage and apoptosis; Fc-mediated ADCC/ADCP also contribute, with additional bystander killing from the membrane-permeable payload.
Autologous T cells genetically engineered to express a chimeric antigen receptor targeting GPRC5D and CD19, redirecting T-cell cytotoxicity against malignant plasma cells and B-lineage/myeloma subclones.
Autologous T cells engineered to express a chimeric antigen receptor recognizing GPRC5D and CD19 on malignant plasma cells and B-lineage/myeloma subclones; antigen engagement activates CAR signaling, triggering T‑cell activation, cytokine release, and perforin/granzyme-mediated cytotoxicity to eradicate tumor cells and reduce antigen escape.
CAR T cells bind GPRC5D on target cells, activating CAR signaling and T‑cell cytolysis via perforin/granzyme (and death‑receptor) pathways, killing the GPRC5D+ cells.
Bispecific IgG1-like anti-HER2 monoclonal antibody targeting ECD2 and ECD4; induces HER2 clustering/internalization, blocks signaling, and activates ADCC/ADCP/CDC.
Zanidatamab is a bispecific IgG1 monoclonal antibody that binds two non-overlapping HER2 extracellular domains (ECD2 and ECD4), promoting HER2 clustering and internalization/downregulation, blocking HER2 signaling and dimerization, and leveraging Fc-mediated effector functions (ADCC, ADCP, CDC) to kill HER2-overexpressing tumor cells.
Zanidatamab binds HER2 on tumor cells and its Fc region recruits immune effectors, inducing ADCC (NK cells), ADCP (macrophages), and CDC (complement), leading to killing of HER2-expressing cells; it also blocks HER2 signaling and promotes internalization/downregulation.
Bispecific IgG1-like anti-HER2 monoclonal antibody targeting ECD2 and ECD4; induces HER2 clustering/internalization, blocks signaling, and activates ADCC/ADCP/CDC.
Zanidatamab is a bispecific IgG1 monoclonal antibody that binds two non-overlapping HER2 extracellular domains (ECD2 and ECD4), promoting HER2 clustering and internalization/downregulation, blocking HER2 signaling and dimerization, and leveraging Fc-mediated effector functions (ADCC, ADCP, CDC) to kill HER2-overexpressing tumor cells.
Zanidatamab binds HER2 (ECD2/ECD4) on target cells and engages immune effectors via its Fc to induce ADCC and ADCP, and can activate complement (CDC), leading to lysis and phagocytosis of HER2+ cells; signaling blockade/internalization contribute but cytotoxicity is via Fc-mediated effector functions.