Fig. 2
From: A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function
Anti-tumor activity of TIGIT-28 F4-transduced T cells. a Human PBLs expressing the F4 TCR were transduced with either TIGIT-28 (TMTi) or TIGIT-28 (TM28), TIGIT-STOP (truncated control) or mock (control). These cells were co-cultured with different melanoma line targets as indicated (x-axis). TNFα secreted in the co-culture supernatant was measured by ELISA. Cytokine concentrations were normalized for each target cell line (with or w/o CD155) to the secretion observed in the positive control Ctrl/F4 group in co-culture with the parental cell line (with an average TNF-α secretion of 4601 pg/ml for 888A2 and 3250 pg/ml for SK-MEL23). These results are presented as mean + SEM of three independent experiments, performed with three different donors (*: p < 0.05, calculated using a Student’s paired t-test). b Human PBLs expressing the F4 TCR were transduced with TIGIT-28 (TMTi) or mock transduced (Ctrl) and were co-cultured with different melanoma line targets as indicated. IFNγ secreted in the co-culture supernatant was measured by ELISA. As earlier, cytokine concentrations were normalized for each target cell line (with or w/o CD155) to the secretion observed in the positive control Ctrl/F4 group (with an average IFNγ secretion of 4620 pg/ml for 888A2 and 3350 pg/ml for SK-MEL23). These results are presented as mean + SEM of six independent experiments, performed with at least five different donors (*:p < 0.05, calculated using a Student’s paired t-test). c-d Similarly, engineered T-cells were co-cultured with different melanoma lines as indicated without TGFβ (c) or with 1.25 ng/ml of TGFβ (d). IL-2 secreted in the co-culture supernatant was measured by ELISA and its concentration was normalized for each target cell line (with or w/o CD155) to the secretion observed in the positive control Ctrl/F4 group (with an average IL-2 secretion of 488 pg/ml for 888A2 and 87 pg/ml for SK-MEL23 without TGFβ; and an average IL-2 secretion of 133 pg/ml for 888A2 and 67 pg/ml for SK-MEL23). These results are presented as mean + SEM of four independent experiments, performed with four different donors (*: p < 0.05, calculated using a Student’s paired t-test)