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. 2019 Jul 25;27(11):1878–1891. doi: 10.1016/j.ymthe.2019.07.013

Figure 5.

Figure 5

Tumor Inhibition by Systemic Injection of ICOS Agonist Targeted to the Tumor

(A) B16-MR1 and B16/F10 tumors were implanted contralaterally in the same mice, and MRP1-ICOS aptamer or Apt8a were injected intravenously to measure aptamer accumulation in each tumor by qRT-PCR using specific primers for the aptamers. (B) Accumulation of MRP1-ICOS aptamer and Apt8 in each tumor (n = 3). Data are expressed as the mean ± SEM. (C) B16-MRP1 melanoma tumors were implanted subcutaneously in C57/BL6 mice. On days 4, 9, and 11 after tumor implantation, mice were injected intraperitoneally with CTLA-4 blockade antibody (9H10) and subcutaneously with B16/F10 irradiated cells as vaccine (VAX); on days 9, 10, 11, 12, and 14, MRP1-ICOS bi-specific aptamer was injected intravenously. (D) Tumor growth kinetics represented as average of tumor volume of each group. Data are expressed as the mean ± SEM. (E) Percentage of tumor volume change after treatment initiation (PBS saline control mice in black; VAX with isotype and Apt ctrl in light gray; VAX with CTLA4 Ab and Apt Ctrl in darker gray; VAX with CTLA4 Ab and Apt MRP1-ICOS in red). (F) Overall survival of mice treated as described in (C). (The experiments were repeated twice with similar results.) **p < 0.01.