Fig. 8: Potent efficacy of indisulam in combination with anti-GD2 in immune competent mice.
From: RBM39 degrader invigorates innate immunity to eradicate neuroblastoma despite cancer cell plasticity
a Uniform Manifold Approximation and Projection (UMAP) of integrated scRNA-seq data from controls (n = 2) and indisulam-treated (n = 1) samples from the Th-MYCN/ALKF1178L models. b UMAP highlights the major cell types (left) and the bar plot shows the proportions of different cell types in control and indisulam samples (right). c Left shows the percentage of immune cells (CD45) in tumors treated with vehicle (n = 3) and indisulam (n = 3) for 5 days, analyzed by flow cytometry. Right shows the percentage of different types of immune cells in tumors treated with vehicle and indisulam for 5 days, analyzed by flow cytometry. Data are presented as Mean +/− SEM. P value calculated with two-sided, unpaired t test. d Individual tumor volume for each group treated with vehicle (n = 11), indisulam (n = 8), anti-GD2 (n = 6), combination (n = 8). Th-MYCN/ALKF1178L mice were treated with the indicated doses and schedule. e The Kaplan-Meier survival for transgenic MYCN/ALKF1178L mice treated with vehicle, anti-GD2, indisulam, combination as shown in (d), with indicated p values (log-rank test) for comparisons of each group. f Individual Dbh-iCre;LSL-MYCN tumor volume treated with vehicle (n = 5), indisulam (n = 5), anti-GD2 (n = 5), combination (n = 5). The Dbh-iCre;LSL-MYCN syngeneic mice treated with 100 mg/kg of indisulam via tail vein injection, every 4 days with a total of 4 doses. The anti-GD2 mAb (300 μg/mouse) is given on the next day after indisulam treatment. g Kaplan-Meier survival for the Dbh-iCre; LSL-MYCN syngeneic mice as shown in (f), with indicated p values (log-rank test) for comparisons of each group. h Individual Th-MYCN tumor volume treated with vehicle (n = 6), temozolomide (TMZ, n = 4), indisulam (n = 6), anti-GD2 (n = 6), combination of indisulam and anti-GD2 (n = 6). The TMZ-resistant Th-MYCN syngeneic mice were treated with indisulam as d (10 mg/kg, 5 days on and 2 days off for 2 weeks), and anti-GD2 (15 μg/mouse, on day 1 and day 5), TMZ (6 mk/kg for 5 days). Data are presented as Mean +/− SEM. i Kaplan-Meier survival for the Th-MYCN syngeneic mice as shown in (h), with indicated p-values (log-rank test) for comparisons of each group. Source data are provided as a Source Data file.
