Fig. 7: TIM3-ProIL2V2 could control tumor in humanized tumor model.

A, B Female Human Havcr2 knockin mice (n = 5/group) were inoculated with 5 × 10⁵ MC38 tumor cells and i.p. treated with 20 μg human TIM3-ProIL2V2 on day 14 and 17 after tumor inoculation. Tumor volume (A), and survival (B) were recorded as indicated. C MC38 bearing female Human Havcr2 knockin mice were treated with 20 μg human TIM3-ProIL2V2 on day 14 and 17 after tumor inoculation. 30 days after treatment, cured mice (n = 4/group) were re-challenged with 2 × 10⁶ MC38 cells. D 3 × 10⁶ CD3⁺ T cells from the spleens of C57BL/6 mice or Human Havcr2 knockin mice (n = 6/group) were adoptively transferred to MC38 bearing female Rag1^−/− mice 5 days after tumor inoculation. 10 μg TIM3-ProIL2V2 or human TIM3-ProIL2V2 was administrated on day 12 and 15 after tumor inoculation. E Female NSG mice (n = 5/group) were subcutaneously inoculated with 2 × 10⁶ A431 tumor cells. Mice were i.v. injected with 10⁷ human PBMC for human immunity construction on day 7 after tumor inoculation. Tumor-bearing mice were treated with 20 μg human TIM3-ProIL2V2 on days 12, 15, and 18 after tumor inoculation. Tumor volume (E) was measured as indicated. F, G Mice (n = 6/group) were i.v. injected with 10⁷ human PBMC for human immunity construction on day 7 after tumor inoculation. Tumor-bearing mice were treated with 20 μg human TIM3-ProIL2V2 on days 12 after tumor inoculation. The mice were sacrificed and tumor tissues were collected 72 h after TIM3-ProIL2V2 treatment. The number of intratumoral total CD8⁺ T cells, TIM3⁻CD8⁺T cells, TIM3⁺CD8⁺ T cells (F) and stem-like CD8⁺ T cells (TIM3⁻PD-1⁺TCF1⁺CD8⁺ T cells) (G) were measured by flow cytometric analysis. Data are shown as mean ± SEM and representative of two to three independent experiments. P value was determined by unpaired two-tailed t tests (A, C–G). Statistical analysis of survival curve was compared using a log-rank test (B).