Triple-Combination Immunogenic Nanovesicles Reshape the Tumor Microenvironment to Potentiate Chemo-Immunotherapy in Preclinical Cancer Models.

ABSTRACT: Immune checkpoint blockade (ICB) therapies have had a tremendous impact on cancer therapy. However, most patients harbor a poorly immunogenic tumor microenvironment (TME), presenting overwhelming de novo refractoriness to ICB inhibitors. To address these challenges, combinatorial regimens that employ chemotherapies and immunostimulatory agents are urgently needed. Here, a combination chemoimmunotherapeutic nanosystem consisting of a polymeric monoconjugated gemcitabine (GEM) prodrug nanoparticle decorated with an anti-programmed cell death-ligand 1 (PD-L1) antibody (αPD-L1) on the surface and a stimulator of interferon genes (STING) agonist encapsulated inside is developed. Treatment with GEM nanoparticles upregulates PD-L1 expression in ICB-refractory tumors, resulting in augmented intrat

SUBMITTER: Shi X 

PROVIDER: S-EPMC10214259 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature