Figure 5
Figure 5. Superior antitumor effect of Akt-inhibited MiHA-specific CD8+ T cells. (A) NSG mice received an intrafemural (IF) injection with UM9 multiple myeloma cells expressing luciferase. On day 1, mice were treated with 50 000 MACS-enriched MiHA-specific CD8+ T cells after culture with (17% CCR7+CD45RO+; n = 8) or without Akt inhibitor (12% CCR7+CD45RO+; n = 9). To support engraftment, CD4+ T cells (0.3 × 106) were co-infused, resulting in a CD4:MiHA-specific T-cell ratio of 1:6. Mice were vaccinated once per week with DCs and received IL-15 every 2 to 3 days. Nontreated mice (n = 8) received only IL-15. From day 7 to day 35, bioluminescence imaging (BLI) was performed once per week to determine the tumor load, after which mice were monitored for survival. (B) BLI images on day 35 and (C) quantified signal corrected for background of the tumor-injected femur over time. Statistical analysis was performed by using a 2-way ANOVA followed by a Bonferroni post hoc test. (D) Survival of mice was analyzed according to a Mantel-Cox test; significance shown compared with no treatment. *P < .05; ***P < .001.

Superior antitumor effect of Akt-inhibited MiHA-specific CD8+ T cells. (A) NSG mice received an intrafemural (IF) injection with UM9 multiple myeloma cells expressing luciferase. On day 1, mice were treated with 50 000 MACS-enriched MiHA-specific CD8+ T cells after culture with (17% CCR7+CD45RO+; n = 8) or without Akt inhibitor (12% CCR7+CD45RO+; n = 9). To support engraftment, CD4+ T cells (0.3 × 106) were co-infused, resulting in a CD4:MiHA-specific T-cell ratio of 1:6. Mice were vaccinated once per week with DCs and received IL-15 every 2 to 3 days. Nontreated mice (n = 8) received only IL-15. From day 7 to day 35, bioluminescence imaging (BLI) was performed once per week to determine the tumor load, after which mice were monitored for survival. (B) BLI images on day 35 and (C) quantified signal corrected for background of the tumor-injected femur over time. Statistical analysis was performed by using a 2-way ANOVA followed by a Bonferroni post hoc test. (D) Survival of mice was analyzed according to a Mantel-Cox test; significance shown compared with no treatment. *P < .05; ***P < .001.

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