Figure 1

Inhibition of mouse and human colon tumor growth by intratumoral treatment with JCXH-211. (A) The srRNA drug substance of JCXH-211 is composed of Cap0 (m7Gppp-), 5’ untranslated region (UTR), alphavirus nonstructural protein (NSP) coding sequences (NSP1-4), subgenomic promoter (SGP), a single-chain IL-12p70 coding sequence, 3’UTR, and poly(A) tail. (B,C) MC38 tumor-bearing mice were treated intratumorally three times at a 7-day interval with mouse IL-12 srRNA-LNP complex (JCXH-211 m) at indicated doses. (B) Tumor volume at indicated time points after first treatment was plotted. (C) Survival was plotted using the Kaplan–Meier curve and analyzed using the log-rank test. (D) At 46 days after the first treatment, indicated numbers of mice from JCXH-211m-treated groups in (C) showed tumor regression and were rechallenged with the same MC38 tumors on contralateral side. No additional treatment was given after tumor rechallenge. The naive control group was a group of naïve mice with MC38 tumor implantation without treatment. (E,F) Humanized mice with patient-derived xenograft tumors were treated intratumorally once weekly for three weeks with human IL-12 srRNA-LNP complex (JCXH-211h) at indicated doses. (E) Tumor volume after the first treatment was plotted. (F) At 3 days after last treatment, tumor-infiltrating lymphocytes were analyzed by flow cytometry. The levels of CD3 + CD56- cells (CD3 + T cells), CD19 + cells (B cells), CD56 + CD16 + cells (NK cells), and CD3 + CD56 + CD16 + cells (NKT cells) in human CD45 + cell population of xenograft tumors were plotted. Individual data points in (B,D–F) represent mean ± SEM. The difference in tumor volume and immune cell population among groups were analyzed statistically by (B,D,E) two-way ANOVA with multiple comparison test and (F) one-way ANOVA with multiple comparison test. *P < 0.05; **P < 0.01; ***P < 0.001; ns not significant (P > 0.05).