免疫检查点抑制治疗抗体已经显示出对几种癌症具有明显的活性，但对于定位于脑部的恶性肿瘤则不太有效，部分原因是由于血脑屏障的保护作用。作者假设一种新化合物NEO100经动脉内注射能够安全、可逆地打开血脑屏障，以实现针对脑部的免疫检查点抑制治疗抗体的治疗活性。 实验采用移植小鼠神经胶质母细胞瘤或黑色素瘤细胞的免疫能力小鼠，对其进行NEO100的单次动脉注射，打开其血脑屏障。以小鼠免疫抗PD-1/PD-L1鼠源单抗为药物，该药物可经由NEO100注射，也可以单独静脉内注射。用于定量测定这些抗体的脑内渗透以及CD8 + T细胞浸润肿瘤微环境的水平，并监测动物的生存状况。 动脉内注射NEO100使免疫检查点抑制治疗抗体在大脑中积累增加，并伴随更多的T细胞出现。在两种恶性肿瘤模型中，单次注射NEO100同时使用抗体可以导致动物长期存活。在没有NEO100的情况下进行抗体治疗则不太有效。 动脉内NEO100打开了血脑屏障，促进免疫检查点抑制治疗抗体进入大脑肿瘤，使其产生治疗活性，并提高T细胞的招募水平。

Immune checkpoint-inhibitory therapeutic antibodies have shown striking activity against several types of cancers but are less effective against brain-localized malignancies, in part due to the protective effect of the blood-brain barrier (BBB). The authors hypothesized that intraarterial (IA) delivery of a novel compound, NEO100, has the potential to safely and reversibly open the BBB to enable brain-targeted therapeutic activity of checkpoint-inhibitory antibodies.Immunocompetent mice with syngeneic glioblastoma or melanoma cells implanted into their brains were subjected to a single IA injection of NEO100 to open their BBB. One dose of murine anti-PD-1/PD-L1 antibody was either coinjected with NEO100 or separately injected intravenously. Brain penetration of these antibodies and levels of CD8+ T cell infiltrate into the tumor microenvironment were quantitated and animal survival was monitored.IA NEO100 enabled the increased accumulation of checkpoint-inhibitory antibodies in the brain, along with greater numbers of T cells. In both malignancy models, a single intervention of IA NEO100 combined with antibody resulted in the long-term survival of animals. Antibody treatment in the absence of NEO100 was far less effective.BBB opening by IA NEO100 facilitates brain tumor access by checkpoint-inhibitory antibodies and enables their therapeutic activity, along with increased levels of T-cell recruitment.