Figure 2.
Pola enhances the antitumor efficacy of glofitamab through modulation of CD20 expression. (A) Experimental design of the in vivo efficacy study. Humanized BRGS-CD47 mice with SC SU-DHL-8 tumors were randomized into 5 groups (12 mice each). Mice were treated with either vehicle (histidine buffer), SUD of glofitamab (0.5-1 mg/kg), Pola (1 mg/kg), or glofitamab in combination with Pola (1 mg/kg) using the same dosing as in monotherapy groups. All treatments were administered IV according to the displayed schedule. All groups received Gpt (30 mg/kg). Four scout animals per group were taken on day 22 for ex vivo analysis, and the study was terminated at day 38. (B) Average tumor volumes are illustrated as mean + SEM for all treatment groups over time. Tumor-free mice are indicated as x/8. (C) Body weight kinetics are illustrated as mean + SEM in all groups. (D) Ex vivo flow cytometry analysis of tumors from scout animals reveals normalized CD8+ and CD4+ T-cell counts and the frequency of Ki-67+ cells in the CD45+/CD3− population. (E) Representative IHC staining for Ki-67 in 2 individual tumors at scout time point is shown for all groups (left). Images were captured using a VS120 Virtual Slide Microscope (Olympus). Quantification of Ki-67+ cells per total cells is illustrated (right), using Tissue Studio software (Definiens) for cell quantification. Bars represent means + SEM, and dots indicate individual mouse values. (F-G) Representative human CD3 and CD20 IHC staining of representative tumors at the scout time point is found for all groups. Upper row, lower magnification; lower row, higher magnification. Images were captured using a VS120 Virtual Slide Microscope (Olympus). Quantification of CD3+ or CD20+ cells per total cells is shown (right in panels F-G), using Tissue Studio software (Definiens) for cell quantification. Bars represent means + SEM, and dots indicate individual mouse values. Statistical analysis was performed using 1-way ANOVA, and significant P values are indicated as follows: ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Gpt, Gazyva pretreatment; M1, mouse 1; M2, mouse 2.

Pola enhances the antitumor efficacy of glofitamab through modulation of CD20 expression. (A) Experimental design of the in vivo efficacy study. Humanized BRGS-CD47 mice with SC SU-DHL-8 tumors were randomized into 5 groups (12 mice each). Mice were treated with either vehicle (histidine buffer), SUD of glofitamab (0.5-1 mg/kg), Pola (1 mg/kg), or glofitamab in combination with Pola (1 mg/kg) using the same dosing as in monotherapy groups. All treatments were administered IV according to the displayed schedule. All groups received Gpt (30 mg/kg). Four scout animals per group were taken on day 22 for ex vivo analysis, and the study was terminated at day 38. (B) Average tumor volumes are illustrated as mean + SEM for all treatment groups over time. Tumor-free mice are indicated as x/8. (C) Body weight kinetics are illustrated as mean + SEM in all groups. (D) Ex vivo flow cytometry analysis of tumors from scout animals reveals normalized CD8+ and CD4+ T-cell counts and the frequency of Ki-67+ cells in the CD45+/CD3 population. (E) Representative IHC staining for Ki-67 in 2 individual tumors at scout time point is shown for all groups (left). Images were captured using a VS120 Virtual Slide Microscope (Olympus). Quantification of Ki-67+ cells per total cells is illustrated (right), using Tissue Studio software (Definiens) for cell quantification. Bars represent means + SEM, and dots indicate individual mouse values. (F-G) Representative human CD3 and CD20 IHC staining of representative tumors at the scout time point is found for all groups. Upper row, lower magnification; lower row, higher magnification. Images were captured using a VS120 Virtual Slide Microscope (Olympus). Quantification of CD3+ or CD20+ cells per total cells is shown (right in panels F-G), using Tissue Studio software (Definiens) for cell quantification. Bars represent means + SEM, and dots indicate individual mouse values. Statistical analysis was performed using 1-way ANOVA, and significant P values are indicated as follows: ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. Gpt, Gazyva pretreatment; M1, mouse 1; M2, mouse 2.

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