Fig. 5: SYNB1891 treatment triggers efficacious antitumor immunity and immunological memory.
From: Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity
a On Study days 1, 4, and 7, B16.F10 tumor-bearing mice were treated i.t. with either saline (control), SYNB1891 or Control EcN lacking the Pfnrs-dacA circuit. Tumor growth data is shown with the ratio of complete responders (C.R.). (**P = 0.0058 (blue stars—indicated group vs EcN), ****P < 0.0001 (pink stars—indicated group vs SYNB1891) one-way ANOVA with Tukey’s multiple comparisons tests for Day 14; **P = 0.0078 (pink stars—EcN vs SYNB1891, two-tailed unpaired Student’s t test. Individual tumor volumes are presented in Supplementary Fig. 5a). b B16.F10 tumor-bearing mice were treated as described in (a), with additional treatment group receiving three i.t. doses of 50μg smSTING agonist. Long-term survival is shown (**P = 0.006, ***P = [0.0004–0.0006], Mantel–Cox log-rank comparisons for the indicated groups, see Supplementary Fig. 5d, e for tumor growth data). c A20 tumor-bearing mice were treated as described in (a) with saline or varying quantities of SYNB1891. Tumor growth data and ratio of C.R. are shown (**P = 0.0014 (blue stars—indicated group vs 108 CFUs SYNB1891), ***P = 0.0004 (pink stars—indicated group vs 5 × 108 CFUs SYNB1891) ****P < 0.0001 (orange stars—indicated group vs 109 CFUs SYNB1891) one-way ANOVA with Tukey’s multiple comparisons tests for Day 21, see Supplementary Fig. 6a, b for individual tumor volumes and long-term survival). d A20 tumor-bearing mice were treated as described in (a) with saline or SYNB1891-cmR (SYNB1891 with chloramphenicol resistance gene). T cells were depleted by administration of anti-CD4 or anti-CD8 antibodies, isotype antibody injected as control. Long-term survival is shown. (*P = 0.041, ****P < 0.0001, N.S. = not significant, Mantel–Cox log-rank comparisons). e Mice treated as described in (c) and remained tumor free by Study day 50 were rechallenged by subcutaneous injection of A20 cells on the contralateral flank alongside naïve age-matched controls. Tumor growth data is shown (Individual tumor volumes are presented in Supplementary Fig. 6c). a–e n = 10 mice per group. a, c, e Mean and s.e.m. are shown. Data are representative of two (b, d, e) and three (a, c) independent experiments.
