In this study, to enhance the therapeutic efficacy of anti-PD-1, we established a novel concept of vascular disruption and normalization dependent on VDAs (CA4-NPs) + VEGF/VEGFR2 inhibitors (DC101) to regulate the imbalance between CD8+ T cells and tumor burden, following a two-step treatment regimen (Scheme 1). This evidence concerns the gene KDR and neoplasm.