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Fig. 3 M7824 inhibits tumor growth and metastasis and provides long-term antitumor immunity.
M7824 inhibits tumor growth and metastasis and provides long-term antitumor immunity. (A and B) Effect of M7824 on tumor growth. Tumor volume (in cubic millimeters) of Jh mice (n = 12 to 13 per treatment) (A) orthotopically inoculated with 0.25 × 106 EMT-6 cells (day −7) and μMt− mice (n = 8 per treatment) (B) intramuscularly inoculated with 0.5 × 106 MC38 cells (day −7) and treated intravenously with isotype control (133 or 400 μg), trap control (164 μg), anti–PD-L1 (133 or 400 μg), M7824 (164 or 492 μg), or trap control (164 μg) + anti–PD-L1 (133 μg) three times a week for 2 weeks (A) or on days 0 and 2 (B). Means ± SEM are shown. (C and D) Number of tumor nodules in the lungs (C) and incidence of metastases in BALB/c mice (D) orthotopically injected with 0.25 × 106 EMT-6 cells (day −7) and treated (n = 21 per group) with a single dose of isotype control (400 μg), trap control (492 μg), anti–PD-L1 (400 μg), or M7824 (492 μg). The mice were sacrificed when isotype control mice reached 1000-mm3 tumor volume. Data from individual mice and means are shown; P values by unpaired t test. (E and F) Percent surviving mice and tumor rechallenge; mice were sacrificed when tumor volume reached ≈2500 mm3. (E) Percent surviving Jh mice orthotopically injected in the right mammary pad with 0.25 × 106 EMT-6 cells (day −7) and treated (n = 9 mice per group) with M7824 (492 μg; days 0 and 14) or isotype control (133 μg; days 0, 7, and 14). For rechallenge, M7824-cured (n = 9) or treatment-naive mice (n = 10) were subcutaneously injected with 0.25 × 105 EMT-6 cells (218 days after final treatment). Tumor volume was measured twice weekly. (F) Percent surviving μMt− mice intramuscularly injected with 0.5 × 106 MC38 cells (day −7) and treated (n = 10 mice per group) with M7824 (492 μg) or isotype control (400 μg) on days 0, 2, 4, 7, 9, and 11. M7824-cured or treatment-naive mice (n = 8 and 10, respectively) were subcutaneously injected with 0.1 × 106 MC38 cells (77 days after final treatment). Tumor volume was measured on days 7, 10, 14, and 18. Means ± SEM are shown. *P ≤ 0.05 and ****P ≤ denote a significant difference relative to an equimolar dose of M7824. Yan Lan et al., Sci Transl Med 2018;10:eaan5488 Published by AAAS
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