Figure 3.

NDNB1182 enhanced ICB efficacy in the PPS syngeneic prostate cancer model. (A) Growth curves of Myc-CaP tumors treated with isotype IgG or ICB (anti-PD1 plus anti-CTLA4) administered intraperitoneally (i.p.) at 10mg/kg, twice/week. N=9/group. (B) Growth curves of Myc-CaP tumors treated with vehicle, Ganetespib (25mg/kg, i.p. daily) or NDNB1182 (50mg/kg, i.p. daily). N=10 tumors/group at the start of the treatment. (C) Survival curves for mice bearing Myc-CaP tumors and treated with vehicle, Ganetespib or NDNB1182. N=5/group. (D) Growth curves of PPS tumors treated with vehicle control (N=6), NDNB1182 (50mg/kg, i.p. daily; N=6), ICB (anti-PD1 plus anti-CTLA4, 10mg/kg, i.p., twice/week; N=10), or concurrent NDNB1182 plus ICB (N=8). In (A, B, D), the randomized groups on day 0 of the treatment showed no significant difference based on statistical tests (for (A) two groups at day 0, P=0.8238 based on Mann Whitney test; for (B) three groups at day 0, P=0.4265 based on ANOVA test; for (D) four groups at day 0, P= 0.5561 based on ANOVA test). (E) Representative images and quantification results for CD8α immunohistochemistry on PPS tumors treated with the four regimens. The tumor regions (“T”) and the margin contours are denoted. N=5 for each condition. Image analysis and quantification was performed with ImageJ following a published protocol (59), where DAB signals were normalized to the number of nuclei present in the images. Scale bar 200µm. (F) Body weight changes of mice treated with vehicle, NDNB1182, or NDNB1182 plus ICB. (G) Representative H&E staining images of liver from vehicle-treated and NDNB1182-treated mice. Scale bar 50µm. (H) Quantification results for cleaved caspase 3 immunohistochemistry on liver and spleen tissues from vehicle-treated and NDNB1182-treated mice. In (A–H), data represent mean ± SEM. #P>0.05; *P<0.05, **P<0.01, ****P<0.0001, Student’s t-test. In (B, D–F), one-way ANOVA test result was shown in red (#P>0.05; ****P<0.0001). In (C), #P>0.05; *P<0.05, logrank test.