Fig. 5: LIPU/MB increases PD-1 antibody brain concentration.

a Scheme showing the experimental procedure for nivolumab concentrations measurement via ELISA in BBB-intact brains, comparing sonicated to non-sonicated mice. b Fluorescent images of mouse brains from 4 groups that received fluorescein, nivolumab, with and without LIPU/MB obtained after 1 and 4 h. c, d Bar plots showing the nivolumab concentration in plasma (c) and the brain (d) in the following groups: LIPU/MB, nivolumab without LIPU/MB, nivolumab with LIPU/MB after 1 hour, and nivolumab with LIPU/MB after 4 h. n = 3 mice for LIPU/MB and nivolumab without LIPU/MB, n = 5 mice for LIPU/MB+nivo 1 h, and n = 4 mice for LIPU/MB+nivo 4 hr. All samples were derived from biologically independent mice from 1 experiment. e (left) Therapeutic scheme and (right) Kaplan-Meier curve of CT-2A-bearing mice treated with aPD-1 delivered with and without LIPU/MB. (n = 10 mice treated with ISO Ab, n = 9 mice treated with aPD-1 group, n = 9 mice treated with LIPU/MB + aPD-1). P values by Log-rank test. f Bar plot showing the pembrolizumab levels in plasma before and 48 h after immunotherapy. n = 2 pre-treatment and 2 post-treatment plasma samples from 2 GBM patients. g (left) Bar plot showing the pembrolizumab concentration in pre-treatment (n = 2) and on-treatment (n = 7) GBM samples obtained 48 h after immunotherapy administration. (right) Dot plot representing the concentration of pembrolizumab in sonicated and non-sonicated peritumoral brain regions obtained after 48 h of immunotherapy administration. n = 2 non-sonicated and 3 sonicated peritumoral brain samples from 2 GBM patients. h Bar plot representing pembrolizumab concentration fold change in peritumoral regions. n = 3 sonicated and 2 non-sonicated peritumoral brain samples from 2 GBM patients. P values in c and d were derived from one-way ANOVA with post hoc Tukey’s multiple comparisons test. Source data are provided as a Source Data file. Data are presented as mean ± s.d. in c, d, f, g and h.