As demonstrated in our treatment study using the intracranial JIMT-1-BR3 tumor model (i.e., complete remission in five of six animals by homogeneous ADC 6 versus no complete remission by heterogeneous ADC 7), a decrease in the effective DAR by heterogeneous conjugation could be further prominent in grade 1–3 gliomas and HER2-positive brain metastatic tumors, in which BBB disruption is less significant than in GBM (Gril et al., 2020; Yonemori et al., 2010). This evidence concerns the gene ERBB2 and central nervous system cancer.