1. Fig. 6 Innate and adaptive immunity, but not ADCC, contributes to M7824 antitumor activity.
Innate and adaptive immunity, but not ADCC, contributes to M7824 antitumor activity. (A) μMt− mice were injected intramuscularly with 0.5 × 106 MC38 cells on day −7 and treated (n = 10 mice per group) on day 0 with isotype control (400 μg), M7824 (492 μg), or M7824 (492 μg) dosed with anti-murine CD4 (GK1.5; 100 μg), anti-murine CD8 (2.43; 100 μg), anti-murine CD4 + anti-murine CD8 (100 μg each), or anti-murine asialo GM1 (ASGM1; 50 μl). All injections were intravenous, except for ASGM1, which was intraperitoneal. Anti-murine antibodies were injected on day 0, and M7824 and isotype control were injected on days 1, 3, and 5. Tumor volumes (in cubic millimeters) were measured twice weekly and are presented as mean ± SEM. (B) Effect of M7824 on PBMC-mediated antibody-dependent cellular cytotoxicity (ADCC) against tumor cells. PBMCs from a human donor were cultured with 51Cr-labeled A431 human epidermoid carcinoma cells for 4 hours in the presence of different concentrations of M7824, anti–PD-L1, aglycosylated M7824, or isotype control. 51Cr release from labeled target cells was measured with a Wallac MicroBeta Trilux Liquid Scintillation Counter, and the percent lysis was determined. Data were fit to a four-parameter dose-response curve. The data shown are representative of five different human donors. (C) μMt− mice were injected intramuscularly with 0.5 × 106 MC38 cells on day −7 and treated (n = 15 mice per group) on day 0 with isotype control (133 μg), M7824 (55 or 164 μg), or aglycosylated M7824 (55 or 164 μg) on days 0, 2, and 4. Tumor volumes (in cubic millimeters) were measured twice weekly and are presented as mean ± SEM. ****P ≤ denotes a significant difference relative to M7824 treatment.
Yan Lan et al., Sci Transl Med 2018;10:eaan5488
Published by AAAS