Tumor-Targeted Inhibition of Monocarboxylate Transporter 1 Improves T-Cell Immunotherapy of Solid Tumors.

ABSTRACT: Export of lactic acid from glycolytic cancer cells to the extracellular tumor milieu has been reported to enhance tumor growth and suppress antitumor immunity. In this study, a pH-activatable nanodrug is reported for tumor-targeted inhibition of monocarboxylate transporter-1 (MCT1) that reverses lactic acid-induced tumor immunosuppression. The nanodrug is composed of an MCT1 inhibitor (AZD3965) loaded inside the ultra-pH-sensitive nanoparticles (AZD-UPS NPs). AZD-UPS NP is produced by a microfluidics method with improved drug loading efficiency and optimal nanoparticle size over sonication methods. The nanodrug remains as intact micelles at pH 7.4 but rapidly disassembles and releases payload upon exposure to acidic pH. When combined with anti-PD-1 therapy, AZD-UPS NP leads to potent tumor

SUBMITTER: Huang T 

PROVIDER: S-EPMC7674253 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature