Fig. 5

Genomic TGFβ RII disruption in CAR T-cells specific for MSLN enhances their cytokine secretion. TGFβ at any dose inhibits cytokine secretion of MSLN-specific WT CAR 4-1BBζ T-cells. A IL-2, B IFNγ, C TNFα, D GM-CSF, E Granzyme B, in the presence of antigen presenting iDCs as APCs. Of importance, amount of cytokines in TGFβRII KO CAR T-cells remain unimpaired and stable even at a very high dose of exogenous TGFβ. Cytokine secretion in either WT or KO groups proved to be antigen specific here as well. P values were determined by two-way Anova using multiple comparison test. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. In all experiments, mean ± SD of three technical replicates are given and experiments, involving T cells, are repeated for at least three donors