Autologous CD19-directed CAR T-cell therapy using a CD19 scFv with CD28/CD3ζ signaling domains, engineered to constitutively secrete interleukin-18 (IL-18) to enhance Th1/IFN-γ responses, cytotoxicity, proliferation, and persistence against CD19+ B-ALL.
Autologous T cells engineered to express a CD19-specific CAR with CD28/CD3ζ signaling (19-28z) that triggers T-cell activation and cytotoxic killing of CD19+ B-ALL cells upon antigen engagement. The cells are further engineered to constitutively secrete IL-18, which enhances Th1/IFN-γ signaling, boosts T and NK cell activation, cytotoxicity, proliferation, and persistence, and modulates the tumor microenvironment to improve anti-leukemic activity.
YES
DIRECT
CD19-directed CAR T cells bind CD19 on target cells and, upon CD28/CD3zeta signaling, directly kill them via perforin/granzyme-mediated cytolysis and Fas-FasL apoptosis; IL-18 secretion enhances T/NK activation and persistence.
Autologous CD19-directed CAR T-cell therapy using a CD19 scFv with CD28/CD3ζ signaling domains, engineered to constitutively secrete interleukin-18 (IL-18) to enhance Th1/IFN-γ responses, cytotoxicity, proliferation, and persistence against CD19+ B-ALL.
Autologous T cells engineered to express a CD19-specific CAR with CD28/CD3ζ signaling (19-28z) that triggers T-cell activation and cytotoxic killing of CD19+ B-ALL cells upon antigen engagement. The cells are further engineered to constitutively secrete IL-18, which enhances Th1/IFN-γ signaling, boosts T and NK cell activation, cytotoxicity, proliferation, and persistence, and modulates the tumor microenvironment to improve anti-leukemic activity.
NO
INDIRECT
IL18R1-expressing cells are not targeted for killing. The CAR T cells kill CD19+ cells via CAR-triggered cytotoxicity (perforin/granzyme, FasL), while secreted IL-18 binds IL18R1 on immune cells to enhance their activity.
Autologous CD19-directed CAR T-cell therapy using a CD19 scFv with CD28/CD3ζ signaling domains, engineered to constitutively secrete interleukin-18 (IL-18) to enhance Th1/IFN-γ responses, cytotoxicity, proliferation, and persistence against CD19+ B-ALL.
Autologous T cells engineered to express a CD19-specific CAR with CD28/CD3ζ signaling (19-28z) that triggers T-cell activation and cytotoxic killing of CD19+ B-ALL cells upon antigen engagement. The cells are further engineered to constitutively secrete IL-18, which enhances Th1/IFN-γ signaling, boosts T and NK cell activation, cytotoxicity, proliferation, and persistence, and modulates the tumor microenvironment to improve anti-leukemic activity.
NO
INDIRECT
The CAR targets CD19, not IL18RAP; secreted IL-18 engages IL18RAP to activate immune cells and modulate the microenvironment, but does not directly kill IL18RAP-expressing cells.
An antibody–drug conjugate composed of a humanized anti-HER2 monoclonal antibody (trastuzumab) linked via a cleavable linker to a membrane-permeable topoisomerase I inhibitor payload (DXd). It binds HER2, mediates ADCC, is internalized, and releases DXd to inhibit topoisomerase I, leading to DNA damage and apoptosis with a bystander effect.
A HER2-targeting monoclonal antibody (trastuzumab) linked via a cleavable linker to a membrane-permeable topoisomerase I inhibitor payload (DXd). After HER2 binding and internalization, the linker is cleaved and DXd is released to inhibit topoisomerase I, causing DNA damage, cell-cycle arrest, and apoptosis; Fc-mediated ADCC and a bystander killing effect also contribute.
YES
DIRECT
The ADC binds HER2, is internalized, and releases the topoisomerase I inhibitor DXd, causing DNA damage and apoptosis; Fc-mediated ADCC and a bystander effect also contribute.
An antibody–drug conjugate composed of a humanized anti-HER2 monoclonal antibody (trastuzumab) linked via a cleavable linker to a membrane-permeable topoisomerase I inhibitor payload (DXd). It binds HER2, mediates ADCC, is internalized, and releases DXd to inhibit topoisomerase I, leading to DNA damage and apoptosis with a bystander effect.
A HER2-targeting monoclonal antibody (trastuzumab) linked via a cleavable linker to a membrane-permeable topoisomerase I inhibitor payload (DXd). After HER2 binding and internalization, the linker is cleaved and DXd is released to inhibit topoisomerase I, causing DNA damage, cell-cycle arrest, and apoptosis; Fc-mediated ADCC and a bystander killing effect also contribute.
NO
INDIRECT
This ADC targets HER2, not topoisomerase I. After HER2 binding and internalization, the DXd payload is released and inhibits topoisomerase I to cause DNA damage and apoptosis (with ADCC and bystander effects). Thus, killing is directed by HER2 expression, not by expression of topoisomerase I itself.