Fig. 6: Allogeneic CD19-CAR NK cells with HLA-ABC knockdown and PD-L1 or SCE overexpression evade host immune cell rejection and control tumor growth in vivo. | Nature Communications

Fig. 6: Allogeneic CD19-CAR NK cells with HLA-ABC knockdown and PD-L1 or SCE overexpression evade host immune cell rejection and control tumor growth in vivo.

From: Selective HLA knockdown and PD-L1 expression prevent allogeneic CAR-NK cell rejection and enhance safety and anti-tumor responses in xenograft mice

Fig. 6

a Schema of the experimental protocol. Allogeneic NK cells without transduction (group 1) or transduced with lentivectors expressing CD19 CAR (group 2), #1 + CD19 CAR + PD-L1 (group 3), or #1 + CD19 CAR + SCE (group 4), were mixed with equal numbers of host PBMCs (4 million), and adoptively transferred into recipient NSG MHC I/II DKO mice that had been injected (IV) with 0.5 million Raji-luciferase two days earlier. b, c Tumor burden was assessed on day 7, 14, and 21 by BLI (b) and presented as the normalized intensity of BLI (c). Groups 1, 2, 3, and 4 mice are labeled in black, blue, orange, and red, respectively. Data are mean ± s.d. (n = 4 for group 1 and 2, n = 5 for group 3 and 4). d Kaplan–Meier curves showing survival of mice. The numbers indicate the p-values between the indicated two groups. e, f Relative percentages of host NK cells (red bar), allogeneic transduced NK cells (black bar), and allogeneic untransduced NK cells (open bar) before transfer, in the blood at day 14 after transfer (e) and in the blood and tissues at the endpoint (f). g, h CD107a expression in host NK cells (red bar), allogeneic transduced NK cells (black bar), and allogeneic untransduced NK cells (open bar) at day 14 after transfer (g) and in spleen at the endpoint (h). Data in (e–h) are mean ± s.d. from two independent experiments, n = 9 for group 1 and 2, and n = 10 for group 3 and 4, at day 14 n = 8 for all four groups at the endpoint. i, j CD69 expression in host CD8+ (open bar) and CD4+ T (gray bar) cells in blood at day 14 after transfer (i) and in spleen at the endpoint (j). Data are mean ± s.d. with 5 mice for each group at day 14 and at the endpoint. At least 5000 hCD45+ cells were collected per sample for analysis. Two-way ANOVA with Tukey’s multiple comparisons and Log-rank test were performed between different groups to determine the statistical difference in (c and d), respectively. The p-values are shown for the indicated comparisons. Figure 6a is created in Biorender.

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