CU06-1004-Induced Vascular Normalization Improves Immunotherapy by Modulating Tumor Microenvironment via Cytotoxic T Cells

Blocking the immune evasion mechanism of tumor cells has become an attractive means for treating cancers. However, usage a drug such as nivolumab (αPD-1), which blocks programmed cell death protein 1 (PD-1), turned out to be only effective against certain types cancer. Especially, vascular abnormal structures deter delivery route by leakage and cause poor perfusion were considered environment unfavorable T checkpoint blockade (ICB) within microenvironment (TME). Herein, we report stabilization blood vessels endothelial dysfunctional blocker CU06-1004, modified TME showed synergistic effects with immunotherapy anti-PD-1 antibody. CU06-1004 combination therapy consistently prolonged survival tumor-bearing mice decreasing growth. T-cell infiltration increased in tumors group, cytotoxic CD8 + activity parenchyma upregulated compared monotherapy. Tumor inhibition was associated reduced hypoxia vessel density central region tumor. These correlated significantly enhanced expression IFN gamma PD-L1 tumors. Taken together, our findings suggest that is potential candidate capable improving therapeutic efficacy through beneficial changes TME.