Autologous T cells retrovirally transduced to express a glypican-3 (GPC3)–specific chimeric antigen receptor, engineered to provide autocrine IL-15 and IL-21 signaling and to include an inducible caspase-9 (iCasp9) safety switch.
Autologous T cells are engineered to express a glypican-3 (GPC3)-specific chimeric antigen receptor that recognizes GPC3 on tumor cells and activates T-cell cytotoxicity; co-expression of IL-15 and IL-21 provides autocrine signaling to enhance proliferation, survival, and persistence; an inducible caspase-9 (iCasp9) safety switch enables rapid elimination of the cells upon administration of a dimerizer drug.
NO
INDIRECT
IL-2/15 receptor beta (CD122) is not the CAR target. These CAR T cells kill GPC3-positive cells via CAR-activated cytolysis (perforin/granzyme); IL-15/IL-21 provide autocrine support and do not mediate killing of IL-2/15Rβ-expressing cells.
Autologous T cells retrovirally transduced to express a glypican-3 (GPC3)–specific chimeric antigen receptor, engineered to provide autocrine IL-15 and IL-21 signaling and to include an inducible caspase-9 (iCasp9) safety switch.
Autologous T cells are engineered to express a glypican-3 (GPC3)-specific chimeric antigen receptor that recognizes GPC3 on tumor cells and activates T-cell cytotoxicity; co-expression of IL-15 and IL-21 provides autocrine signaling to enhance proliferation, survival, and persistence; an inducible caspase-9 (iCasp9) safety switch enables rapid elimination of the cells upon administration of a dimerizer drug.
NO
INDIRECT
These CAR T cells kill GPC3+ tumor cells via T‑cell effector functions (perforin/granzyme). IL‑15Rα is not recognized by the CAR; IL‑15/IL‑21 provide autocrine support to the T cells, not target-cell killing.
Autologous T cells retrovirally transduced to express a glypican-3 (GPC3)–specific chimeric antigen receptor, engineered to provide autocrine IL-15 and IL-21 signaling and to include an inducible caspase-9 (iCasp9) safety switch.
Autologous T cells are engineered to express a glypican-3 (GPC3)-specific chimeric antigen receptor that recognizes GPC3 on tumor cells and activates T-cell cytotoxicity; co-expression of IL-15 and IL-21 provides autocrine signaling to enhance proliferation, survival, and persistence; an inducible caspase-9 (iCasp9) safety switch enables rapid elimination of the cells upon administration of a dimerizer drug.
NO
INDIRECT
FKBP12(F36V)-iCasp9 is a safety switch in the engineered CAR T cells; when a dimerizer (e.g., rimiducid) is given, it induces caspase-9 dimerization and apoptosis of the CAR T cells themselves, not target tumor cells.
Autologous T cells retrovirally transduced to express a glypican-3 (GPC3)–specific chimeric antigen receptor, engineered to provide autocrine IL-15 and IL-21 signaling and to include an inducible caspase-9 (iCasp9) safety switch.
Autologous T cells are engineered to express a glypican-3 (GPC3)-specific chimeric antigen receptor that recognizes GPC3 on tumor cells and activates T-cell cytotoxicity; co-expression of IL-15 and IL-21 provides autocrine signaling to enhance proliferation, survival, and persistence; an inducible caspase-9 (iCasp9) safety switch enables rapid elimination of the cells upon administration of a dimerizer drug.
YES
DIRECT
Upon administration of a dimerizer drug, iCasp9 in the engineered CAR T cells is activated, triggering the caspase cascade and inducing rapid apoptosis of the iCasp9-expressing cells.
Small-molecule dimerizer used to activate the inducible caspase-9 safety switch to rapidly eliminate CAR T cells in the event of toxicity.
Rimiducid (AP1903) is a small-molecule dimerizer that binds engineered FKBP12(F36V) domains fused to inducible caspase-9 in gene-modified T cells, inducing caspase-9 dimerization and activation, which triggers downstream caspase-3/7–mediated apoptosis to rapidly eliminate the modified cells as a safety switch in case of toxicity.
YES
DIRECT
Rimiducid binds the engineered FKBP12(F36V) domains in the iCasp9 switch, dimerizing and activating caspase-9 and triggering downstream caspase-3/7–mediated apoptosis of the modified cells.