Anti-PD-L1 scFv-secreting fifth-generation GD2-CAR T cells enhance antitumor function against GD2-low retinoblastoma.

Fifth-generation GD2-CAR T cells secreting anti-PD-L1 scFv show superior cytotoxicity against GD2-low retinoblastoma cells at low effector-to-target ratios.

• Why it matters: Retinoblastoma treatment faces challenges from chemoresistance and antigen loss, limiting the effectiveness of current GD2-targeted CAR T cells and risking vision loss.
• What they did: Researchers engineered a fifth-generation GD2-CAR (GD2-CAR5) that secretes anti-PD-L1 scFv, confirming surface expression and PD-L1 blockade, and tested its activity against high- and low-antigen-density RB cells in vitro.
• The result: GD2-CAR5 T cells maintained cytotoxicity and cell numbers longer than fourth-generation CAR T cells during repeated stimulation, suggesting enhanced potential for treating GD2-low retinoblastoma.