Figure 6.
Exploring and evaluating novel chemotherapy-free combination partners. (A) Experimental design of the in vivo pharmacodynamic (PD) study in humanized NSG mice bearing subcutaneous OCI-Ly18 tumors. The mice were divided into 2 experimental groups, each consisting of 8 mice. One group received a vehicle control (histidine buffer), whereas the other was treated with Gpt (30 mg/kg) followed by glofitamab (0.15 mg/kg). The compounds were administered IV after the displayed timeline, and the study concluded on day 19. (B) Ex vivo flow cytometry analysis was conducted on the tumors at study termination. Normalized counts of CD4+ and CD8+ T cells, Treg counts, and the frequency of CD28+ CD4+ or CD8+ intratumoral T cells are illustrated. In addition, phenotypic analysis of CD8+ T cells was performed, assessing 4-1BB, PD-1, TIM-3, and LAG-3 (from left to right) expression. Bars illustrate means + SEM, and dots indicate values of individual mice. Statistical analysis was performed using unpaired t test, and significant P values are indicated as follows: ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. (C) Experimental design of the in vivo combination efficacy study. (D) Humanized NSG mice with subcutaneous OCI-Ly18 tumors were allocated to 9 experimental groups (10 mice per group) and were treated with vehicle (histidine buffer), glofitamab monotherapy (0.5 mg/kg), or combination treatments with either CD19–4-1BBL (1 mg/kg), CD19-CD28 (1 mg/kg), α-CD25 (10 mg/kg), or PD1-Lag3 (3 mg/kg). Triple combinations of glofitamab + CD19–4-1BBL with either PD1-LAG3, α-CD25, or CD19-CD28 were evaluated. All groups received Gpt (30 mg/kg) on study day 9. Compounds were administered IV according to the displayed timeline, and the study was terminated on day 43. (E) Waterfall plots for day 19 (left), day 26 (middle), and day 40 (right) illustrate individual tumor sizes normalized to the tumor volume of each mouse at the start of treatment on day 9. Positive values indicate tumor growth, whereas negative values indicate regression. Each bar represents an individual mouse at the respective time points, with colors indicating different treatments. The indicated values represent the percentage of mice revealing tumor regression at each time point. Statistical analysis was performed using 1-way ANOVA, and significant P values are indicated as follows: ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. FC, fold change; n.d., not determined.

Exploring and evaluating novel chemotherapy-free combination partners. (A) Experimental design of the in vivo pharmacodynamic (PD) study in humanized NSG mice bearing subcutaneous OCI-Ly18 tumors. The mice were divided into 2 experimental groups, each consisting of 8 mice. One group received a vehicle control (histidine buffer), whereas the other was treated with Gpt (30 mg/kg) followed by glofitamab (0.15 mg/kg). The compounds were administered IV after the displayed timeline, and the study concluded on day 19. (B) Ex vivo flow cytometry analysis was conducted on the tumors at study termination. Normalized counts of CD4+ and CD8+ T cells, Treg counts, and the frequency of CD28+ CD4+ or CD8+ intratumoral T cells are illustrated. In addition, phenotypic analysis of CD8+ T cells was performed, assessing 4-1BB, PD-1, TIM-3, and LAG-3 (from left to right) expression. Bars illustrate means + SEM, and dots indicate values of individual mice. Statistical analysis was performed using unpaired t test, and significant P values are indicated as follows: ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. (C) Experimental design of the in vivo combination efficacy study. (D) Humanized NSG mice with subcutaneous OCI-Ly18 tumors were allocated to 9 experimental groups (10 mice per group) and were treated with vehicle (histidine buffer), glofitamab monotherapy (0.5 mg/kg), or combination treatments with either CD19–4-1BBL (1 mg/kg), CD19-CD28 (1 mg/kg), α-CD25 (10 mg/kg), or PD1-Lag3 (3 mg/kg). Triple combinations of glofitamab + CD19–4-1BBL with either PD1-LAG3, α-CD25, or CD19-CD28 were evaluated. All groups received Gpt (30 mg/kg) on study day 9. Compounds were administered IV according to the displayed timeline, and the study was terminated on day 43. (E) Waterfall plots for day 19 (left), day 26 (middle), and day 40 (right) illustrate individual tumor sizes normalized to the tumor volume of each mouse at the start of treatment on day 9. Positive values indicate tumor growth, whereas negative values indicate regression. Each bar represents an individual mouse at the respective time points, with colors indicating different treatments. The indicated values represent the percentage of mice revealing tumor regression at each time point. Statistical analysis was performed using 1-way ANOVA, and significant P values are indicated as follows: ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. FC, fold change; n.d., not determined.

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