Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy.

ABSTRACT: Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated tumors to synergize with immune checkpoint blockade. However, even with high doses of radiation, RT has rarely elicited systemic immune responses. Herein, we report the design of two porous Hf-based nanoscale metal-organic frameworks (nMOFs) as highly effective radioenhancers that significantly outperform HfO₂, a clinically investigated radioenhancer in vitro and in vivo. Importantly, the combination of nMOF-mediated low-dose RT with an anti-programmed death-ligand 1 antibody effective

SUBMITTER: Ni K 

PROVIDER: S-EPMC6003951 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature