Autologous, lentiviral-transduced PSMA-directed CAR T-cell therapy with a humanized J591-derived anti-PSMA scFv, CD2 costimulatory domain, and dual armoring via a dominant-negative TGFβ receptor and a PD1.CD28 switch receptor.
Autologous T cells are lentivirally engineered to express a PSMA-specific CAR (humanized J591 scFv) with a CD2 costimulatory domain. The cells are dually armored with a dominant-negative TGF-beta receptor to resist TGF-beta–mediated immunosuppression and a PD1.CD28 switch receptor that converts PD-1 inhibitory signals into CD28 costimulation, enhancing activation, persistence, and cytotoxic killing of PSMA-expressing tumor cells.
NO
INDIRECT
The CAR targets PSMA, not TGF-beta 1. The dominant-negative TGF-beta receptor only blocks TGF-beta signaling in the CAR T cells and does not mediate killing of TGF-beta 1–expressing cells.
Subcutaneous bispecific T‑cell–engaging monoclonal antibody that binds BCMA on malignant plasma cells and CD3 on T cells to redirect T‑cell cytotoxicity against BCMA‑positive myeloma cells.
Bispecific T‑cell–engaging monoclonal antibody that binds BCMA on myeloma/plasma cells and CD3 on T cells, forming an immune synapse that activates and redirects T‑cell cytotoxicity (perforin/granzyme) to kill BCMA‑positive cells.
NO
INDIRECT
CD3 is on T cells; elranatamab binds CD3 to activate and recruit T cells, which kill BCMA-positive myeloma cells via perforin/granzyme. CD3+ cells are not targeted for killing.
Autologous, lentiviral-transduced PSMA-directed CAR T-cell therapy with a humanized J591-derived anti-PSMA scFv, CD2 costimulatory domain, and dual armoring via a dominant-negative TGFβ receptor and a PD1.CD28 switch receptor.
Autologous T cells are lentivirally engineered to express a PSMA-specific CAR (humanized J591 scFv) with a CD2 costimulatory domain. The cells are dually armored with a dominant-negative TGF-beta receptor to resist TGF-beta–mediated immunosuppression and a PD1.CD28 switch receptor that converts PD-1 inhibitory signals into CD28 costimulation, enhancing activation, persistence, and cytotoxic killing of PSMA-expressing tumor cells.
NO
INDIRECT
These CAR T cells target PSMA, not TGF-β2. They kill PSMA-expressing cells via CAR-mediated T‑cell cytotoxicity (perforin/granzyme). The dominant‑negative TGF‑β receptor only renders the T cells resistant to TGF‑β.
Autologous, lentiviral-transduced PSMA-directed CAR T-cell therapy with a humanized J591-derived anti-PSMA scFv, CD2 costimulatory domain, and dual armoring via a dominant-negative TGFβ receptor and a PD1.CD28 switch receptor.
Autologous T cells are lentivirally engineered to express a PSMA-specific CAR (humanized J591 scFv) with a CD2 costimulatory domain. The cells are dually armored with a dominant-negative TGF-beta receptor to resist TGF-beta–mediated immunosuppression and a PD1.CD28 switch receptor that converts PD-1 inhibitory signals into CD28 costimulation, enhancing activation, persistence, and cytotoxic killing of PSMA-expressing tumor cells.
NO
INDIRECT
TGF-beta3 is not the CAR target. The CAR recognizes PSMA and kills PSMA+ cells via T‑cell cytotoxicity (perforin/granzyme). The dominant-negative TGF-beta receptor only blocks TGF-beta signaling in the CAR T cells and does not direct killing of TGF-beta3–expressing cells.
An investigational antibody–drug conjugate (ADC) in which a monoclonal antibody targeting an undisclosed tumor-associated antigen is linked to a cytotoxic payload; after antigen binding and internalization, the payload is released intracellularly to kill tumor cells.
Monoclonal antibody binds an undisclosed tumor-associated surface antigen, is internalized, and a cleavable linker releases a cytotoxic payload inside the cancer cell, resulting in intracellular cytotoxicity (e.g., DNA damage or microtubule disruption) and tumor cell death.
YES
DIRECT
The ADC binds the tumor-associated surface antigen, is internalized, and a cleavable linker releases a cytotoxic payload inside the cell (e.g., DNA-damaging or microtubule-disrupting agent), leading to target cell death.