Fig. 1: CD38-specific synapse stabilizing receptor (SSR) harbouring a truncated LAT endodomain improves CLL1.CAR-mediated killing of antigen-low AML.
From: Enhancing CAR- and TCR-mediated targeting of cancer via an immune synapse-stabilizing receptor
A A schematic showing interaction between CLL1.CAR and CD38.SSR. CAR and SSR configurations are denoted on the right B Representative flow plots showing co-expression of CAR and SSRs on day7 post co-transduction (TD). SSR expression was measured by detection of a surrogate maker truncated NGFR. C Residual tumor counts after a 3-day culture of CD38+ Molm13 (AML) and CCRF-CEM (T-ALL) with non-transduced T cells (NT) or SSR T cells at an E:T ratio 1:4. Data represent 3 donors. P values were determined using one way ANOVA with Tukey’s correction for multiple comparisons. Bar graphs show mean+S.E.M. (*P < 0.05, **P < 0.01, ***P < 0.001. ns, non-significant). D Histograms showing CLL1 and CD38 levels in indicated cell lines. E Residual tumor counts and T-cell expansion after a 3-day co-culture of Molm13 and CCRF-CEM with CAR T cells at a E:T ratio 1:4. Data represent 6 donors from 3 independent experiments. P values were determined using one way ANOVA with Tukey’s correction for multiple comparisons. Bar graphs show mean + S.E.M. (*P < 0.05, **P < 0.01, ***P < 0.001. ns, non-significant). F Histograms showing CLL1 and CD38 levels in pre-sorted THP1 and CLL1-low THP1 post-sorting. G Residual tumor counts and fold T-cell expansion after 3 day culture at a E:T ratio 1:4. Data represent 6 donors from 2 independent experiments. P values were determined using one way ANOVA with Tukey’s correction for multiple comparisons. Bar graphs show mean + S.E.M. (*P < 0.05. ns, non-significant). H CD38 expression in the parental and knock-out line of Molm13. I Residual tumor counts and fold T-cell expansion after 3 day culture at a E:T ratio 1:4. Data represent 4 donors from 2 independent experiments. P values were determined using one way ANOVA with Tukey’s correction for multiple comparisons. Bar graphs show mean + S.E.M. (*P < 0.05, **P < 0.01, ***P < 0.001. ns, non-significant). (*P < 0.05, **P < 0.01. ns, non-significant).
