AGTR1 inhibitor nanoconjugate boosts chemo, immunotherapies in cancers

INDICATION: Pancreatic cancer; breast cancer

Mouse studies suggest a nanoconjugate based on the generic ATGR1 inhibitor valsartan could enhanced the efficacy of chemotherapies and checkpoint inhibitors in pancreatic and metastatic breast cancers. The nanoconjugate consists of valsartan linked to an acetal-based polymer that degrades and releases the drug more rapidly in the acidic tumor microenvironment than at normal physiological pH. In a mouse model of pancreatic cancer, the nanoconjugate plus the chemotherapy 5-fluorouracil (5-FU) decreased tumor size compared with 5-FU alone. In a mouse model of lung-metastatic breast cancer, the nanoconjugate plus paclitaxel increased survival compared with either agent alone. Also in the model and in five other mouse models of primary and metastatic breast cancer, the nanoconjugate plus anti-PD-1 and anti-CTLA-4 mAbs decreased tumor size compared with mAb combination. In the metastatic models, the nanoconjugate plus the two mAbs increased survival. Next steps include testing the valsartan-based nanoconjugate or nanoconjugates based on other AGTR1 inhibitors in mouse models of other solid tumor types...