Intravenous anti-PD-L1 monoclonal antibody immunotherapy that blocks PD-L1 to disrupt the PD-1/PD-L1 checkpoint and restore cytotoxic T-cell antitumor activity.
Human IgG1 anti-PD-L1 monoclonal antibody that binds PD-L1 and blocks its interaction with PD-1, inhibiting checkpoint signaling to restore cytotoxic T-cell activity; also capable of inducing antibody-dependent cellular cytotoxicity against PD-L1-expressing tumor cells.
YES
DIRECT
IgG1 Fc mediates ADCC by NK cells (and other FcγR+ effectors) against PD-L1–expressing cells; checkpoint blockade also restores T-cell killing (indirect).
Allogeneic donor-derived T cells genetically modified via lentiviral transduction to express a CD33-specific CAR with a CD8 hinge, 4-1BB costimulatory, and CD3ζ signaling domains, including a truncated EGFR (EGFRt) safety tag for potential ablation; designed to target CD33+ AML cells.
Allogeneic T cells are lentivirally engineered to express a CD33-specific CAR with 4-1BB costimulation and CD3ζ signaling. Upon binding CD33 on AML cells, the CAR activates T-cell cytotoxicity and proliferation, leading to targeted lysis of CD33+ cells; a truncated EGFR tag enables cetuximab-mediated ablation as a safety switch.
YES
DIRECT
CAR binding to CD33 activates CD3ζ/4-1BB signaling in the engineered T cells, triggering targeted lysis of CD33+ cells via perforin/granzyme-mediated cytotoxicity (and Fas/FasL apoptosis).
Allogeneic donor-derived T cells genetically modified via lentiviral transduction to express a CD33-specific CAR with a CD8 hinge, 4-1BB costimulatory, and CD3ζ signaling domains, including a truncated EGFR (EGFRt) safety tag for potential ablation; designed to target CD33+ AML cells.
Allogeneic T cells are lentivirally engineered to express a CD33-specific CAR with 4-1BB costimulation and CD3ζ signaling. Upon binding CD33 on AML cells, the CAR activates T-cell cytotoxicity and proliferation, leading to targeted lysis of CD33+ cells; a truncated EGFR tag enables cetuximab-mediated ablation as a safety switch.
NO
INDIRECT
EGFRt is a safety tag on the CAR T cells; the anti-CD33 CAR does not target EGFR. Only if an anti-EGFR antibody (e.g., cetuximab) is administered would EGFRt+ CAR T cells be eliminated via antibody-mediated cytotoxicity, not by the CAR T cells themselves.
EGFR-targeting monoclonal antibody used as a safety 'off switch' to ablate EGFRt-tagged CAR T cells if needed.
Cetuximab is a chimeric IgG1 monoclonal antibody that binds the extracellular domain of EGFR, blocking ligand binding and receptor dimerization to inhibit downstream signaling and cell proliferation. Its Fc can recruit immune effector functions (e.g., ADCC/CDC). In this trial it is used as a safety off-switch by binding the truncated EGFR (EGFRt) tag on CAR T cells to enable their targeted elimination.
YES
DIRECT
Cetuximab binds EGFR on the cell surface and its IgG1 Fc recruits immune effectors to mediate ADCC and complement-dependent cytotoxicity, killing EGFR-expressing cells (used here to ablate EGFRt-tagged CAR T cells).
EGFR-targeting monoclonal antibody used as a safety 'off switch' to ablate EGFRt-tagged CAR T cells if needed.
Cetuximab is a chimeric IgG1 monoclonal antibody that binds the extracellular domain of EGFR, blocking ligand binding and receptor dimerization to inhibit downstream signaling and cell proliferation. Its Fc can recruit immune effector functions (e.g., ADCC/CDC). In this trial it is used as a safety off-switch by binding the truncated EGFR (EGFRt) tag on CAR T cells to enable their targeted elimination.
YES
DIRECT
Cetuximab binds the EGFRt tag and, via its Fc domain, engages immune effectors to kill tagged cells through ADCC and complement-mediated lysis (and phagocytosis).