Intravenously administered, such trispecific mAbs with a polyamine unit would cross the endothelium at the BBB via RMT using TfR, and would then be endocytosed in target brain cancer cells through EGFR-mediated endocytosis and elicit anti-cancer activity after endosomal escape or lysosomal escape, probably due to membrane rupture from the proton sponge effect. Here, TFRC is linked to brain cancer.