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. 2021 Aug 30;13(10):e13598. doi: 10.15252/emmm.202013598

Figure 6. Combination of IFN‐γ gene therapy with other immunotherapies enhances anti‐tumoral activity.

Figure 6

  • A–D
    Combination gene therapy with IFN‐α, TNF‐α, and IFN‐γ, expressed from the Tie2 vector platform. CTRL (Tie2.NGFR), two independent experiments, n = 9 mice; IFN‐α, one experiment, n = 2 mice; IFN‐α/IFN‐γ, one experiment, n = 4 mice; IFN‐α/TNF‐α, one experiment, n = 3 mice; IFN‐γ/TNF‐α, two independent experiments, n = 19 mice. (A) Vector copy number (VCN) in peripheral blood at 8 weeks post‐transplantation (mean ± SD). (B) B‐ALL progression in peripheral blood measured as absolute number of OFP+ cells (mean ± SD, each dot represents an individual mouse; *P = 0.0308, ***P = 0.0004, ****P ≤ 0.0001, two‐way ANOVA with Geisser–Greenhouse correction). (C) Percentage of MHC II+ macrophages, identified by F4/80 expression, in the spleen (mean ± SD, each dot represents an individual mouse; *P = 0.0484, **P = 0.0049, ordinary one‐way ANOVA). (D) Percentage of CD8+ T lymphocytes within CD45‐positive and OFP‐negative splenic cells (mean ± SD, each dot represents an individual mouse; *P = 0.0356, ordinary one‐way ANOVA).
  • E–G
    Combination of IFN‐γ gene therapy with immuno‐oncology drugs. CTRL (Tie2.NGFR) + antibody isotype, n = 6 mice; CTRL + αCTLA4 antibody, n = 5 mice; CTRL + αLAG3 antibody, n = 5 mice; CTRL + 1‐methyltryptophan (1‐MT), n = 5 mice; IFN‐γ (Tie2.IFN‐γ) + antibody isotype, n = 7 mice; IFN‐γ + αCTLA4 antibody, n = 7 mice; IFN‐γ + αLAG3 antibody, n = 7 mice; IFN‐γ + 1‐MT, n = 5 mice. (E) B‐ALL progression in the peripheral blood measured as absolute number of OFP+ cells (mean ± SD, each dot represents an individual mouse; ns = not significant, **P = 0.001 (CTRL isotype vs. IFN‐γ + αCTLA4); **P = 0.0022 (CTRL isotype vs. CTRL + αLAG3), ***P ≤ 0.001, ****P ≤ 0.0001; comparisons are against the corresponding isotype, or as indicated by the lines; two‐way ANOVA). (F) Percentage of MHC II+ macrophages, identified by F4/80 expression, in the spleen (mean ± SD, each dot represents an individual mouse; **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001 as compared to CTRL isotype, ordinary one‐way ANOVA). (G) Percentage of CD8+ T lymphocytes within OFP‐negative BM cells (mean ± SD, each dot represents an individual mouse).

Data information: Statistical analyses of panels (C) and (E) are shown in Appendix Tables S7 and S8, respectively.