Figure 4.
p(Man-TLR7-PDS) combination therapy significantly enhances overall survival. C57Bl/6 mice were inoculated with 1 million C1498 cells IV (day 0). For each experiment, combination treatment was administered with 2 mg cytarabine on day 1 followed by 40 μg TLR7 equivalent of p(Man-TLR7-PDS), repeated weekly. Time between injections and number of weeks of treatment varies as described. (A-B) Combination treatment was separated by 24 hours and administered for 4 weeks (n = 6), and mice were tracked for (A) overall survival and (B) change in body weight through first event. (C) Combination treatment was compared in its survival benefit to single-agent efficacy of p(Man-TLR7-PDS) (n = 6). (D) p(Man-TLR7-PDS) combination treatment was compared in its survival benefit to an equivalent TLR7 dose of molecular weight–matched, nonbinding control polymer p(Man-TLR7) in combination with cytarabine. Data are pooled from 2 separate experiments in which combination treatment was separated by 24 hours and administered for 4 weeks (n = 5 each replicate; 10 total). (E) Combination treatment was separated by 6 hours and administered for 1 week and evaluated for its survival event in a single injection context. Data are pooled from 2 separate experiments with identical conditions (n = 5-6 each replicate; 11 total). All data are plotted as mean ± SEM. Statistical analyses were performed using pairwise log-rank (Mantel-Cox) curve comparison for survival with multiple testing correction. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ns, not significant.