Enhanced anti-tumor activity by zinc finger repressor-driven epigenetic silencing of immune checkpoints and TGFBR2 in CAR-T cells and TILs

. To further increase anti-tumor potency in this context, ZFR-expressing lentiviral vectors (LVs) targeting PD-1 and other ICs (LAG-3, TIM-3, and TIGIT) or TGFBR2 were developed, improving significantly the cytotoxic activity in TILs. This strategy highlights the potential to enhance tumor-reactive T cells and improve anti-cancer immunotherapies by epigenetically repressing immunosuppressive factors in the TME using multiplexed ZFRs.