Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy.

ABSTRACT: Despite its success in several clinical trials, cancer immunotherapy remains limited by the rarity of targetable tumor-specific antigens, tumor-mediated immune suppression, and toxicity triggered by systemic delivery of potent immunomodulators. Here, we present a proof-of-concept immunomodulatory gene circuit platform that enables tumor-specific expression of immunostimulators, which could potentially overcome these limitations. Our design comprised de novo synthetic cancer-specific promoters and, to enhance specificity, an RNA-based AND gate that generates combinatorial immunomodulatory outputs only when both promoters are mutually active. These outputs included an immunogenic cell-surface protein, a cytokine, a chemokine, and a checkpoint inhibitor antibody. The circuits triggered select

SUBMITTER: Nissim L 

PROVIDER: S-EPMC5986174 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature