Fig. 5: Moderate activation pattern of KIF-P2 T cells associates with sustained anti-tumor response upon in vivo rechallenge in contrast to strongly activated KIF-sc1. | Nature Communications

Fig. 5: Moderate activation pattern of KIF-P2 T cells associates with sustained anti-tumor response upon in vivo rechallenge in contrast to strongly activated KIF-sc1.

From: High-resolution profile of neoantigen-specific TCR activation links moderate stimulation to increased resilience of engineered TCR-T cells

Fig. 5

a Setting of xenograft neoTCR-TIL-P rechallenge experiment. b Tumor growth kinetics of U698M-mut mg displayed as tumor area (in cm2) on day 17 after second injection of in total 5 × 106 neoTCR-tg T cells (55% TCRmu+ for all groups). For TIL-P-groups, TIL-P from two mice per TCR were pooled. Mean and SEMs for each group display rejection dynamics (n = 5 experimental groups, n = 3 2.5D6; one 2.5D6-control sacrificed earlier). Statistical significance calculated for tumor area on day 17 with one-way ANOVA and Tukey’s multiple comparison test (adjusted p values of TIL-P-KIF-P2 versus 2.5D6: ***p = 0.0001 and TIL-P-KIF-P2 versus -KIF-sc1: ****p < 0.0001). c Kaplan–Meier-survival curve displayed for U698M-tumor-bearing mice injected with TCR-tg T cells (n = 5 for experimental groups, n = 4 for 2.5D6-control; Mantel–Cox test, p = 0.0019). d, e Log2(fold change) is depicted for the ratio KIF-P2:KIF-sc1 for cytokines secreted within 20 h of in vitro co-culture on the day of (re)injection of TIL-P or NEW T cell conditions (d0 of survival experiment) with U698M-mut-mg (E:T = 50,000:50,000). Ratios depicted for NEW (d) and TIL-P (e) cells from three human donors (A, B and C). Mean and min-to-max-range depicted. f Heatmap showing transcriptional expression for selected cytokines detected in bulk-RNAseq on CD8+-enriched neoTCR-tg T cells of donor B normalized to 2.5D6-control (12 h or 24 h stimulation with U698M mut mg or wt mg). Technical triplicates pooled prior to CD8+-enrichment. g Tumor growth kinetics of A2058-mut mg displayed as tumor area (in cm2) until day 15 after injection of 5 × 106 neoTCR-tg T cells (55% TCRmu+ for all groups). Mean values and SEMs display rejection dynamics (n = 5 for experimental groups, n = 7 for TIL-P KIF-P2 and n = 4 for 2.5D6; one 2.5D6-control sacrificed earlier). Statistical significance was calculated for tumor area on day 14 with one-way ANOVA and Tukey’s multiple comparison test (adjusted p values of TIL-P-KIF-P2 versus 2.5D6: **p = 0.0018 and TIL-P-KIF-P2 versus -KIF-sc1: **p = 0.0075). h Kaplan–Meier-survival curve for A2058-tumor-bearing mice injected with TCR-tg T cells (n = 5, n = 7 for TIL-P KIF-P2; Mantel–Cox test, p values of TIL-P-KIF-P2 versus 2.5D6: ***p = 0.0005 and TIL-P-KIF-P2 versus -KIF-sc1: *p = 0.0138).

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