Fig. 1: SAM-FC-mediated induction of tumor regression and long-term immunological memory in tumor-bearing mouse models.
From: Reprogramming the tumor immune microenvironment using engineered dual-drug loaded Salmonella
a Visual representation of the therapeutic mechanism underlying the mode of action of Salmonella (SAM) engineered to express ClyA and FlaB (SAM-FC). b Experimental scheme. Briefly, BALB/c mice were implanted subcutaneously (s.c) with CT26 cells. When tumors reached approximately 120 mm3 (day 0), the mice were randomly divided into five treatment groups: PBS; SAM-E; SAM-FR; SAM-CR; and SAM-FC. Mice received bacteria by intravenous injection (arrow). Bacteria-treated mice were then given Doxy (orally, 1.7 mg/kg) daily from day 3. ( + ) means Doxy was administered. The tumor-eradicated mice (survivors) were s.c rechallenged with CT26 cells on day 90. Naïve age-matched mice were implanted with CT26 cells used as controls. c Average growth curves of primary CT26 tumors [PBS (n = 24), SAM-E (n = 24), SAM-FR(+) (n = 21), SAM-CR (+) (n = 21), and SAM-FC(+) (n = 32)]. All mice were examined from three independent experimental replicates; *P = 0.0149, ****P < 0.0001; ns not significant; two-way ANOVA with Tukey’s multiple comparisons test. d Kaplan-Meier survival curves from (c) [*P = 0.0284, ***P = 0.0001 and ****P < 0.0001; Log-rank (Mantel-Cox) test]. e Average growth curves after CT26 tumor rechallenge [SAM-FR(+) (n = 6), SAM-CR(+) (n = 6), SAM-FC(+) (n = 16), and naïve mice (n = 9)]. All mice were examined from three independent experimental replicates; ****P < 0.0001; ns, not significant; two-way ANOVA with Tukey’s multiple comparisons test. f Experiment scheme. g Average growth curves of primary MC38 tumors [PBS (n = 9), SAM-E (n = 9), SAM-FR(+) (n = 10), SAM-CR(+) (n = 10), and SAM-FC(+) (n = 15)]. All mice were examined from two independent experimental replicates; **P = 0.0015, ***P = 0.0004, ****P < 0.0001; ns not significant; two-way ANOVA with Tukey’s multiple comparisons test. h Kaplan-Meier survival curves from (g) [*P = 0.0240, **P = 0.0017 in PBS vs SAM-CR(+), **P = 0.0014 in SAM-E vs SAM-FR(+), ****P < 0.0001; ns not significant; Log-rank in Mantel-Cox test]. i Average growth curves after MC38 tumor rechallenge [SAM-FR(+) (n = 7), SAM-CR(+) (n = 5 mice), SAM-FC(+) (n = 12), and naïve mice (n = 9 mice)]. All mice were examined from two independent experimental replicates; ***P = 0.0007 in SAM-FC(+) vs SAM-FR(+); ****P < 0.0001; ns, not significant; two-way ANOVA with Tukey’s multiple comparisons test.
