Both a-CTLA-4 and a-PD-1 free mAbs and their combination failed to increase survival compared to PBS treatment (Fig. 7f, g), in line with their inability to cross the BBB (Fig. 2) and increase mouse survival, as well as with the failure of a clinical trial with such mAbs as GBM treatment9. Here, CTLA4 is linked to glioblastoma.