Combined disruption of T cell inflammatory regulators Regnase-1 and Roquin-1 enhances antitumor activity of engineered human T cells

To investigate the effect of Regnase-1 and/or Roquin-1 disruption in engineered primary human T cells, we produced CAR-T cells and TCR-T cells with single genetic disruption of Regnase-1, Roquin-1, or dual disruption of Regnase-1 and Roquin-1. We then performed differential gene expression analysis using data obtained from bulk RNA-seq of 3 different biological donors at baseline. Differential gene expression analysis of bulk RNA-seq data for primary human T cells transduced with either a mesothelin-targeting CAR or NY-ESO-1-targeting TCR, with genetic disruption of Regnase-1, Roquin-1, both Regnase-1 and Roquin-1, or mock control.