Fig. 1

Antitumor effect of combination therapy with hCHST15 siRNA and anti-PD-1 antibody in KPC-implantation model. (A) Experimental design. Mouse KPC cells (5 × 10⁴ cells/mouse) were implanted subcutaneously into syngeneic C57/BL6 mice on day 0. Four groups were conducted: (1) Control (KPC inoculation only) (n = 5), (2) hCHST15 siRNA monotherapy (0.9 mg/mouse) (n = 5), (3) anti-PD-1 antibody monotherapy (aPD-1, RMP1-4, 5 mg/kg/mouse) (n = 5), (4) Combination therapy of hCHST15 siRNA and anti-PD-1 antibody (n = 5). Dosing was performed: Local (intratumoral) injection BIW from day 6 to day 17 (1) Control (KPC inoculation only) (n = 5), (2) hCHST15 siRNA monotherapy (0.9 mg/mouse) (n = 5), (3) anti-PD-1 antibody monotherapy (5 mg/kg/mouse) (n = 5), (4) Combination therapy of hCHST15 siRNA and anti-PD-1 antibody (n = 5). Local [Intratumoral] injections for saline or hCHST15 siRNA were performed BIW from day 6 to 17 (2 weeks), × 4 times in total. Systemic injections for anti-PD-1 antibody of control antibody were performed BIW from day 6 to 17 (2 weeks), × 4 times in total. (B) (left) The HE staining for tumor tissues of 4 groups at day 20. Scale bar = 2.5 mm. Dotted circles show the tumor area. (right) Tumor volume (mm³) was calculated by histology on day 20. CTL: Control (n = 5), siRNA: hCHST15 siRNA monotherapy (n = 5), aPD1: anti-PD-1 antibody monotherapy (n = 5), siRNA + aPD1: hCHST15 siRNA + aPD1 combination therapy (n = 5). One-way ANOVA Bonferroni’s multiple comparison test, *p < 0.05, ***p < 0.001. Mann–Whitney test for 2 groups (aPD1 vs combination), # < 0.05. Tumor growth inhibition (TGI) was calculated as follows; TGI (%) = (1-Ti/Vi) × 100. Ti as the mean tumor volume of the treatment group on day 20. Vi as the mean tumor volume of control group at day 20.