Evorpacept; a SIRPα D1–Fc fusion protein with an inactive Fc that blocks CD47 to enhance macrophage-mediated phagocytosis (ADCP).
Evorpacept (ALX148) is a SIRPα D1–Fc fusion protein with an inactive Fc that binds CD47 on tumor cells, blocking CD47–SIRPα signaling to remove the anti-phagocytic 'don't-eat-me' signal, thereby enhancing macrophage-mediated phagocytosis (ADCP) and promoting downstream anti-tumor T cell responses.
YES
INDIRECT
Blocking CD47–SIRPα removes the 'don’t-eat-me' signal on CD47+ cells, enabling macrophage-mediated phagocytosis (ADCP) and secondary T-cell–mediated killing.
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.
YES
DIRECT
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.
YES
DIRECT
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.
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.
YES
INDIRECT
The ADC binds HER2, is internalized, and releases the DXd payload, which inhibits Top1 to cause DNA damage and apoptosis; Top1 is not the binding target, so Top1-expressing cells are killed only when the payload reaches them (e.g., via HER2-mediated uptake or bystander diffusion).
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.
YES
DIRECT
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.