AZD0901 (CMG901) is an antibody–drug conjugate targeting CLDN18.2; it binds CLDN18.2 on tumor cells, is internalized, and releases a cytotoxic payload to kill CLDN18.2-expressing cells.
Claudin18.2-targeted monoclonal antibody linked via a cleavable linker to MMAE (vedotin). Binds CLDN18.2 on tumor cells, is internalized, and releases MMAE to inhibit tubulin polymerization, causing G2/M arrest and apoptosis in CLDN18.2-expressing cells.
NO
INDIRECT
AZD0901 targets CLDN18.2 on the cell surface; after internalization, the linker is cleaved and MMAE binds beta‑tubulin to disrupt microtubules, causing G2/M arrest and apoptosis in CLDN18.2‑positive cells. Beta‑tubulin itself is not the targeting determinant.
Autologous, genetically modified CAR T-cell therapy targeting mesothelin, engineered with CD28 costimulation, a tuned 1XX CD3ζ signaling domain to balance activation and persistence, and a PD-1 dominant-negative receptor to resist PD-1/PD-L1–mediated inhibition; delivered intraperitoneally for mesothelin-positive esophagogastric adenocarcinoma with peritoneal carcinomatosis.
Autologous T cells engineered to express a mesothelin-specific CAR with CD28 costimulation and a tuned 1XX CD3ζ signaling domain to balance activation and persistence, plus a PD‑1 dominant‑negative receptor that abrogates PD‑1/PD‑L1–mediated inhibition. Upon intraperitoneal delivery, the cells recognize mesothelin on tumor cells and execute cytotoxic killing and cytokine release while resisting checkpoint suppression.
YES
DIRECT
Mesothelin-specific CAR T cells bind mesothelin on target cells and kill via perforin/granzyme release and death-receptor (Fas/FasL) pathways, with cytokine-mediated effects; a PD-1 dominant-negative receptor blocks PD-1/PD-L1 inhibition.
Autologous, genetically modified CAR T-cell therapy targeting mesothelin, engineered with CD28 costimulation, a tuned 1XX CD3ζ signaling domain to balance activation and persistence, and a PD-1 dominant-negative receptor to resist PD-1/PD-L1–mediated inhibition; delivered intraperitoneally for mesothelin-positive esophagogastric adenocarcinoma with peritoneal carcinomatosis.
Autologous T cells engineered to express a mesothelin-specific CAR with CD28 costimulation and a tuned 1XX CD3ζ signaling domain to balance activation and persistence, plus a PD‑1 dominant‑negative receptor that abrogates PD‑1/PD‑L1–mediated inhibition. Upon intraperitoneal delivery, the cells recognize mesothelin on tumor cells and execute cytotoxic killing and cytokine release while resisting checkpoint suppression.
NO
INDIRECT
Killing is triggered by CAR recognition of mesothelin. The PD-1 dominant-negative receptor binds PD-L1 only to block inhibitory signaling and does not confer cytotoxicity against PD-L1–expressing cells.
Autologous, genetically modified CAR T-cell therapy targeting mesothelin, engineered with CD28 costimulation, a tuned 1XX CD3ζ signaling domain to balance activation and persistence, and a PD-1 dominant-negative receptor to resist PD-1/PD-L1–mediated inhibition; delivered intraperitoneally for mesothelin-positive esophagogastric adenocarcinoma with peritoneal carcinomatosis.
Autologous T cells engineered to express a mesothelin-specific CAR with CD28 costimulation and a tuned 1XX CD3ζ signaling domain to balance activation and persistence, plus a PD‑1 dominant‑negative receptor that abrogates PD‑1/PD‑L1–mediated inhibition. Upon intraperitoneal delivery, the cells recognize mesothelin on tumor cells and execute cytotoxic killing and cytokine release while resisting checkpoint suppression.
NO
INDIRECT
The CAR T cells kill mesothelin-expressing cells via CAR-mediated cytotoxicity (perforin/granzymes). The PD-1 dominant-negative receptor blocks PD-1 signaling from PD-L1/PD-L2 to prevent inhibition but does not target PD-L2+ cells for killing.
Intravenous chimeric IgG1 monoclonal antibody against EGFR; blocks ligand binding and receptor dimerization, downregulates EGFR signaling, and can mediate ADCC.
Cetuximab is a chimeric IgG1 monoclonal antibody that binds the extracellular domain of EGFR, blocking ligand binding and receptor dimerization to inhibit downstream MAPK and PI3K–AKT signaling and tumor cell proliferation; its Fc region can also mediate NK cell–driven ADCC against EGFR-expressing cells.
YES
DIRECT
IgG1 Fc engages Fcγ receptors on NK cells to mediate ADCC against EGFR-expressing cells (and can also activate complement-dependent cytotoxicity); signaling blockade is antiproliferative.