Self-blockade of PD-L1 with bacteria-derived outer-membrane vesicle for enhanced cancer immunotherapy.

The checkpoint inhibitor therapy that blocks the Programmed Death-1 (PD-1) and its major ligand PD-L1; has achieved encouraging clinical efficacy in certain cancers. However; the binding of checkpoint inhibitors with other immune cells that express PD-L1 often results in a low response rate to the blockade and severe adverse effects. Herein; we developed a LyP1 polypeptide-modified outer-membrane vesicle (LOMV) loaded with a PD-1 plasmid to achieve self-blockade of PD-L1 in tumor cells. The nanocarriers accumulated in the tumor tissue through OMV-targeting ability and were internalized into the tumor cells via LyP1-mediated target; subsequently delivering PD-1 plasmid into the nucleus; leading to the expression of PD-1 by tumor cells. In addition; a magnetic particle chemiluminescence kit was developed to quantitatively detect the binding rate of PD-1/PD-L1. The self-expressed PD-1 bonded with the PD-L1 expressed by both autologous and neighboring tumor cells; achieving self-blockade. Simultaneously; the outer-membrane protein of LOMV recruited cytotoxic lymphocyte cells and natural killer cells to tumor tissues and stimulated them to secrete IFN-γ; improving the antitumor activity of the PD-1/PD-L1 self-blocking therapy. This article is protected by copyright. All rights reserved.