Skip to main content
. 2023 Nov 29;23(4):421–435. doi: 10.1158/1535-7163.MCT-23-0336

Figure 5.

Figure 5. mXTX301 demonstrates effective peripheral masking and intratumoral pharmacodynamic effects in MC38 syngeneic tumor model. MC38 tumor-bearing mice were treated with the indicated doses of mXTX301 or unmasked control, (A) The spleen size was assessed by a one-way ANOVA with Bonferroni's post hoc pairwise comparison test compared with vehicle (PBS) treated animals (*, P < 0.05; ***, P < 0.0005; ****, P < 0.0001). The data represents mean ± SEM. B, The animals were sacrificed on day 7 (n = 5 mice per group) spleen and tumor were isolated and IFNγ was assessed by MSD assay. IFNγ measurements were log10-transformed and analyzed by one way ANOVA followed by Dunnett multiple comparisons test (***, P = 0.0001; ****, P < 0.0001). C, Immune cells were characterized via flow cytometry. The data are presented as means ± SEM, spleen (n = 5), tumor-treatment groups (n = 5), tumor-vehicle group (n = 4). Statistical significance was determined by one-way ANOVA test followed by Dunnett multiple comparisons test. #, P = 0.05; *, P < 0.05; **, P < 0.01; ***, P < 0.0005; and ****, P < 0.0001 (D) Evaluation of mXTX301 induced gene expression in the MC38 tumors by bulk RNA-seq. Heat map showing relative expression of top mXTX301 differentially expressed genes (N = 10 upregulated and N = 5 downregulated; by P value). Rows (genes) were clustered according to Euclidean distance. Keys above each column (sample)indicate treatment group [vehicle, mXTX301 (0.39 mg/kg), or unmasked control (0.03 mg/kg)]. Box color tracks with z-score-transformed relative expression of each gene across samples (blue, under-expression compared with the mean; red: over-expression compared with the mean) (E) Heat map summarizing results of a pathway enrichment analysis where each box indicates the enrichment significance (-log10 Fisher P value) of a gene set of interest (rows) in the Top 250 most significantly upregulated genes (by P value) computed by comparing tumors after treatment with mXTX301 or unmasked control versus vehicle at Day 7 (columns). Color intensity tracks with significance.

mXTX301 demonstrates effective peripheral masking and intratumoral pharmacodynamic effects in MC38 syngeneic tumor model. MC38 tumor-bearing mice were treated with the indicated doses of mXTX301 or unmasked control, (A) The spleen size was assessed by a one-way ANOVA with Bonferroni's post hoc pairwise comparison test compared with vehicle (PBS) treated animals (*, P < 0.05; ***, P < 0.0005; ****, P < 0.0001). The data represents mean ± SEM. B, The animals were sacrificed on day 7 (n = 5 mice per group) spleen and tumor were isolated and IFNγ was assessed by MSD assay. IFNγ measurements were log10-transformed and analyzed by one way ANOVA followed by Dunnett multiple comparisons test (***, P = 0.0001; ****, P < 0.0001). C, Immune cells were characterized via flow cytometry. The data are presented as means ± SEM, spleen (n = 5), tumor-treatment groups (n = 5), tumor-vehicle group (n = 4). Statistical significance was determined by one-way ANOVA test followed by Dunnett multiple comparisons test. #, P = 0.05; *, P < 0.05; **, P < 0.01; ***, P < 0.0005; and ****, P < 0.0001 (D) Evaluation of mXTX301 induced gene expression in the MC38 tumors by bulk RNA-seq. Heat map showing relative expression of top mXTX301 differentially expressed genes (N = 10 upregulated and N = 5 downregulated; by P value). Rows (genes) were clustered according to Euclidean distance. Keys above each column (sample)indicate treatment group [vehicle, mXTX301 (0.39 mg/kg), or unmasked control (0.03 mg/kg)]. Box color tracks with z-score-transformed relative expression of each gene across samples (blue, under-expression compared with the mean; red: over-expression compared with the mean) (E) Heat map summarizing results of a pathway enrichment analysis where each box indicates the enrichment significance (-log10 Fisher P value) of a gene set of interest (rows) in the Top 250 most significantly upregulated genes (by P value) computed by comparing tumors after treatment with mXTX301 or unmasked control versus vehicle at Day 7 (columns). Color intensity tracks with significance.