Figure 3. Eradication of GBM intracranial tumors, glial scar formation, and enhanced survival of mice induced by ADI-PEG20 in combination with ionizing radiation.
(A–C) Bioluminescence imaging (BLI) of intracranial tumors in mice using an IVIS Lumina II and Living Image software starting from day 13 after injection of GL261-Luc2 tumor cells. (D) Kaplan-Meier survival graph. Median survival times were 27, 47, and 37 days for saline, ADI-PEG20, and ionizing radiation (IR) monotherapy, respectively. Animals treated with combined treatment remained healthy and tumor free beyond 1 year. These animals received IR for 8 weeks and ADI-PEG20 for 13 weeks, after which time treatments were stopped. (E) Two animals from this group were culled on day 140 and brain sections were stained with H&E and for GFAP, showing evidence of histologically apparent glial scarring at the tumor site. Scale bars: 430 μm (left); 200 μm (middle, right). Data were analyzed using 2-way ANOVA with Tukey’s multiple comparison test, and adjusted P values are reported. ***P < 0.001 (saline vs. ADI-PEG20) + IR; §§§P < 0.001 (ADI-PEG20 vs. ADI-PEG20 + IR); ###P < 0.001 (IR vs. ADI-PEG20 + IR).