A. CT2A GBM-bearing mice were treated with either empty control CANDIE (N = 18), CANDI (0.5 mg LCL-161, 0.2 mg R848; N = 25), CANDI + a-PD1 (500 μg LCL-161, 200 μg R848, 200 μg a-PD1 antibody; N = 16) or CANDI with a-CD8 (500 μg LCL-161, 200 μg R848, 200 μg a-CD8; N = 4). Animals were serially imaged (MRI and BLI) until the time of sacrifice (23 days). Note the significant growth retardation with CANDI and CANDI + a-PD1, an effect that was abolished by CD8 depletion. This data and the data from Fig. S12 show that CANDI therapy functions through anti-tumor T cell production of IFNG. B. Shown are representative T1W MR images following administration of gadolinium. Note the substantial therapeutic effect of CANDI and its additive effect with a-PD1 antibody. The differences between CANDI and CANDIE (P = 0.0003) were highly statistically significant. See Fig. S13 and Fig. S14 for details on bioluminescence and additional MR imaging. C. Tumor volumes in the 4 different groups as determined at the time of sacrifice. D. Survival graphs for three different treatment groups. All animals injected with CANDIE (without payload) had died by day 30 after tumor implantations, as expected from the MRI (see panel B). The difference between the CANDI group and the control group injected with empty CANDIE was highly significant (P < 0.0001).