Oncolytic adenovirus programmed by synthetic gene circuit for cancer immunotherapy.

ABSTRACT: Improving efficacy of oncolytic virotherapy remains challenging due to difficulty increasing specificity and immune responses against cancer and limited understanding of its population dynamics. Here, we construct programmable and modular synthetic gene circuits to control adenoviral replication and release of immune effectors selectively in hepatocellular carcinoma cells in response to multiple promoter and microRNA inputs. By performing mouse model experiments and computational simulations, we find that replicable adenovirus has a superior tumor-killing efficacy than non-replicable adenovirus. We observe a synergistic effect on promoting local lymphocyte cytotoxicity and systematic vaccination in immunocompetent mouse models by combining tumor lysis and secretion of immunomodulators. Fur

SUBMITTER: Huang H 

PROVIDER: S-EPMC6805884 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature