Fig. 7: In vivo anti-leukemia efficacy of DN4.99 TCR-T cells against THP-1-CD1c-tumor cells.

DN4.99 TCR-transduced T (DN4.99 TCR-T) cells and non-transduced T cells (T cells), all at 70% CD8⁺/30% CD4⁺, were assessed for the ability to control the progression of THP-1-CD1c acute leukemia in vivo. a NOD.Cg-Prkdcscid IL- 2rgtm1Wjl/SzJ (NSG) mice (n = 15) received intravenous (i.v.) injection of 10⁶ THP-1-CD1c cells co-expressing secreted LUCIA luciferase. Three weeks later the mice were sub-lethally irradiated, followed 24 h later by the transfer of 10⁷ DN4.99 TCR-T cells (red lines/dots), T cells (black lines/squares), or vehicle (gray line/triangles). n = 5 mice/group. b Tumor progression was monitored weekly in blood collections by bioluminescence assay and depicted as the Relative Light Unit (RLU) detected at each time point. Data are represented as mean ± SEM. ****P < 0.0001 determined on AUC by Ordinary one-way ANOVA followed by Tukey’s multiple comparison test. c Kaplan–Meier survival curves show a significant increase in the survival of mice receiving DN4.99 TCR-T cells compared to the control groups. *P = 0.0368 with T cells; *P = 0.0274 with vehicle determined by log-rank (Mantel–Cox) test. d Reduced endpoint liver weight in mice receiving DN4.99 TCR-T cells (red dots) compared to the control groups (non-injected aged-match NSG mice: white dots; mice receiving: T cells, black squares; vehicle, gray triangles), determined at sacrifice (day +46). Data are represented as mean ± SD. *P = 0.01557 with T cells; *P = 0.0224 vehicle determined by Ordinary one-way ANOVA followed by Tukey’s multiple comparison test. e Persistence of DN4.99 TCR-T cells in the liver of mice, determined by flow cytometry at sacrifice. DN4.99 TCR-T cells and THP1-CD1c leukemia cells were identified by mouse (m)TCRβ, human CD3, and GFP expression, respectively, among gated mouse CD45^- mononuclear hepatic cells. Results are representative of 5 independent experiments with independent T cell lines giving comparable results.