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. 2021 Oct 1;9(10):e003464. doi: 10.1136/jitc-2021-003464

Figure 3.

Figure 3

The therapeutic effect of αCD47/PD-L1 mouse surrogates in syngeneic tumor models. (A–C) Antitumor efficacy, survival and body weight post treatment of indicated antibodies in CT26 tumor model. BALB/c mice bearing subcutaneous CT26 tumors were dosed IP with 5 mg/kg of mIgG2a isotype, 5 mg/kg of αmCD47, 5 mg/kg of αmPD-L1, the combination of 5 mg/kg of αmCD47 and 5 mg/kg of αmPD-L1, or 5 mg/kg of mBisAb on days 0, 3, and 7 post-treatment initiation (n=7–8 mice/group). (A) Tumor growth; significance was calculated by two-way ANOVA with Tukey’s multiple comparison test. (B) Kaplan-Meier survival curves post-treatment initiation. (C) Percent of initial body weight reported as a mean±SEM; significance was calculated by two-way ANOVA with Tukey’s multiple comparison test compared with isotype control. (D) BALB/c mice were dosed IP on day 0 and 3 with the same concentration in (A–C). Red blood cells from whole blood on day 5 were counted (n=6–7 mice/group). Significance was calculated by ordinary one-way ANOVA compared with control. (E) Antitumor efficacy in B16F10 tumor model. C57BL/6 mice bearing subcutaneous B16F10 tumors were treated on 9 days post-inoculation with isotype control or mBisAb three times a week for 3 weeks (n=10 mice/group). Significance was calculated by two-way ANOVA with Sidak’s multiple comparison test. (F) Dose-dependent antitumor efficacy in MC38 tumor model. C57BL/6 mice bearing subcutaneous MC38 tumors were treated 7 days postinoculation and dosed IP every 3–4 days for 3 weeks with 10, 20, and 40 mg/kg of mBisAb (n=10 mice/group). Significance was calculated by two-way ANOVA with Tukey’s multiple comparison test. (G–I) Antitumor efficacy following mBisAb treatment and immune cell depletion in MC38 model. MC38-bearing mice were dosed with vehicle (control) or mBisAb every 3–4 days for a total of six doses. Depletion antibodies were administrated IP 1 day prior to treatment with mBisAb and dosed three times a week throughout the study. (n=8–10 mice/group). Significance was calculated by two-way ANOVA with Tukey’s multiple comparison test. (J) C57BL/6 wildtype (WT) and Batf3-/- mice bearing subcutaneous MC38 tumor were dosed IP every 3–4 days for 3 weeks with mBisAb (n=8 mice/group). Significance was calculated by two-way ANOVA with sidak’s multiple comparison test. Asterisks indicate statistical significance (*p<0.05, **p<0.01, ***p<0.001, ****p<0.0001). ANOVA, analysis of variance; αmPD-L1, anti-mouse PD-L1 antibody; αmCD47, anti-mouse CD47 antibody; mBisAb, αCD47/PD-L1 mouse surrogate; IP, intraperitoneally.