Fig. 1: MGA271, 376.96 and TE9 scFv’s mediate divergent CAR-T responses against in vivo models of medulloblastoma and neuroblastoma.
a Schematic of the SFG backbone retroviral constructs. b Schematic of orthotopic, luciferase+ Med8A medulloblastoma tumor model in NSG mice with representative pre-treatment images. The experiment was repeated twice; each treatment group is representative of at least N = 5 animals. c Serial tumor luminescence measurements including at instances of metastatic relapse. d Event (acute tumor burden toxicity)-free survival was compared between the different T cell treatment groups (Log-Rank Mantel–Cox Test 376 x MGA p = 0.018; TE9 x MGA p = 0.056). e Representative pre-treatment images of luciferase+ LAN-1 neuroblastoma tumor model in NSG mice (N = 5). f Serial tumor luminescence measurements for all animals. g Event (tumors exceeding permissible 1 × 109 p/s/cm²/sr threshold prior to cull on ethical grounds)-free survival (log-rank Mantel–Cox test 376 x NT p = 0.0051; TE9 x NT p = 0.0053; MGA x NT p = 0.0296). h Tumors from LAN-1-engrafted animals were collected at cull and processed for flow cytometric analysis to assess live human T cell content of total live cells within the tumor mass (error bars ± SEM, N = 5; Kruskal–Wallis test). i Schematic of metastatic, luciferase+ SKN-A-S neuroblastoma tumor model in NSG mice. j SKN-A-S model: event (acute toxicity from tumor burden)-free survival of non-transduced or TE9 CAR-T cell treatment combined with 1.75 Gy total body irradiation (TBI) (N = 9; log-rank Mantel–Cox test). k Preliminary data from a single experiment of SKN-A-S treatment with 1.75. Gy TBI and MGA271 or 376.96 binder-CAR-T cells. Representative luminescence data over time on the left, and event (acute toxicity from tumor burden)-free survival comparison on the right: 8–9 animals per group; comparisons using a log-rank Mantel–Cox test.
