Figure 7.

Therapeutic Efficacy Observed with ICT and ICV CAR T Cell Administration

ffLuc⁺ PBT030-2 cells (1 × 10⁵) were stereotactically implanted into both the left and right forebrains of NSG mice. Treated mice received either mock-transduced or IL13BBζ T cells (1 × 10⁶ CAR⁺ cells) either ICT or ICV on day 6 (B, C, and E) or day 8 (D and F). (A) Schematic of tumor cell and T cell intracranial injection sites. (B) Representative mice from each group (n = 5 per group) showing relative tumor burden over time using Xenogen Living Image. T cell infusion on day 6 is indicated by the vertical dotted line. (C) Quantification of mean ffLuc flux (+SE) on days 5, 9, 12, 15, and 19 (indicated on the x axis) for each brain hemisphere (left or right) in the untreated (red), ICT-treated (blue), and ICV-treated (green) groups of mice. (D) Representative 0.68× and 5× images of H&E staining of tumors in brains harvested 7 days after IL13BBζ T cell administration either ICT (top) or ICV (bottom). Images such as these were then used to determine length × width calculations of tumor area (mm²) in both the left (L) and right (R) hemispheres of mice treated with either mock-transduced or IL13BBζ T cells as depicted in the graph (mean + SD). *p < 0.0111 when compared to the respective hemisphere and delivery of mock-transduced T cells using the unpaired Student’s t test. (E) Representative 10× images of CD3 IHC stained tumor sites (left versus right) of brains harvested 7 days after IL13BBζ Tcm administration either ICT (top) or ICV (bottom). (F) Kaplan-Meier survival curve demonstrating improved survival for IL13BBζ T cell-treated mice. T cell infusion on day 8 is indicated by the vertical dotted line. Using the log rank (Mantel-Cox) test, p = 0.0018 when comparing IL13BBζ to mock-transduced T cell treatment given either ICT or ICV; p = 0.4187 when comparing IL13BBζ T cell treatment given either ICT or ICV.