Figure 6.
The TCR gene editing approach protects mice from GVHD and ensures a significant survival advantage over TCR gene transfer. Human T-cell chimerism in mice bone marrow (A) and spleen (B) at euthanization, calculated as follows: % of hCD3pos cells/[(% of hCD3pos + % of mCD45pos cells) × 100], detected by flow cytometry. Analysis of mock-transduced (mock-trd), TR, and SE cells injected mice. Each replicate and the means are shown. *P < .05, **P < .01, and ***P < .005 by 1-way ANOVA and Bonferroni’s multiple comparison test. (C) Kaplan Meier curve showing overall survival of untreated (U266, dotted purple line) mice and animals injected with mock-trd (red line), TR (dotted blue line), and SE (light green line) cells. ***P < .005 by log-rank test. (D) Pie charts representing mouse outcome: at time of euthanization animals presented either in good clinical conditions and disease free (alive event-free, red), or with MM marrow infiltration (MM, blue), or with clinical and pathological signs of xenogeneic GVHD (light green), or with both U266 infiltration and GVHD (MM + GVHD, purple). The outcomes of the 4 treatment groups (U266, Mock-trd, TR, and SE) are shown. (E) Histopathological findings at euthanization. Analyses of skin, tongue, heart, lung, kidney, liver, and gut, collected at euthanization for each mouse, fixed in formalin and analyzed blinded by immunohistochemistry for T-cell infiltration. The pathological score ranged from 0 (completely healthy tissue, with no evidence of human T cells) to 3 (substantial and diffuse human lymphocyte infiltration, with subversion of the tissue architecture). Left panel: number of organs with T-cell infiltration (any grade)/mouse. For each animal a grade ranging from 0 to 7 was possible. Results on single animals and means are shown. Mock-trd, TR and SE treated mice are shown. ***P < .005, by 1-way ANOVA and Bonferroni’s multiple comparison test. Right panel: global pathological score for each individual mouse corresponding to the sum of all scores determined for each organ. Each value corresponds to a single animal. Means are also shown. Mock-trd, TR and SE treated mice are shown. ***P < .005, by 1-way ANOVA and Bonferroni’s multiple comparison test.

The TCR gene editing approach protects mice from GVHD and ensures a significant survival advantage over TCR gene transfer. Human T-cell chimerism in mice bone marrow (A) and spleen (B) at euthanization, calculated as follows: % of hCD3pos cells/[(% of hCD3pos + % of mCD45pos cells) × 100], detected by flow cytometry. Analysis of mock-transduced (mock-trd), TR, and SE cells injected mice. Each replicate and the means are shown. *P < .05, **P < .01, and ***P < .005 by 1-way ANOVA and Bonferroni’s multiple comparison test. (C) Kaplan Meier curve showing overall survival of untreated (U266, dotted purple line) mice and animals injected with mock-trd (red line), TR (dotted blue line), and SE (light green line) cells. ***P < .005 by log-rank test. (D) Pie charts representing mouse outcome: at time of euthanization animals presented either in good clinical conditions and disease free (alive event-free, red), or with MM marrow infiltration (MM, blue), or with clinical and pathological signs of xenogeneic GVHD (light green), or with both U266 infiltration and GVHD (MM + GVHD, purple). The outcomes of the 4 treatment groups (U266, Mock-trd, TR, and SE) are shown. (E) Histopathological findings at euthanization. Analyses of skin, tongue, heart, lung, kidney, liver, and gut, collected at euthanization for each mouse, fixed in formalin and analyzed blinded by immunohistochemistry for T-cell infiltration. The pathological score ranged from 0 (completely healthy tissue, with no evidence of human T cells) to 3 (substantial and diffuse human lymphocyte infiltration, with subversion of the tissue architecture). Left panel: number of organs with T-cell infiltration (any grade)/mouse. For each animal a grade ranging from 0 to 7 was possible. Results on single animals and means are shown. Mock-trd, TR and SE treated mice are shown. ***P < .005, by 1-way ANOVA and Bonferroni’s multiple comparison test. Right panel: global pathological score for each individual mouse corresponding to the sum of all scores determined for each organ. Each value corresponds to a single animal. Means are also shown. Mock-trd, TR and SE treated mice are shown. ***P < .005, by 1-way ANOVA and Bonferroni’s multiple comparison test.

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