细菌来源外膜囊泡对 PD-L1 的自阻断用于增强癌症免疫治疗

The checkpoint inhibitor therapy that blocks 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, an LyP1 polypeptide-modified outer-membrane vesicle (LOMV) loaded with a PD-1 plasmid is developed to achieve self-blockade of PD-L1 in tumor cells. The nanocarriers accumulate in the tumor tissue through OMV-targeting ability and are internalized into the tumor cells via the LyP1-mediated target, subsequently delivering PD-1 plasmid into the nucleus, leading to the expression of PD-1 by the tumor cells.

In addition, a magnetic particle chemiluminescence kit is developed to quantitatively detect the binding rate of PD-1/PD-L1. The self-expressed PD-1 bonded with the PD-L1 is expressed by both autologous and neighboring tumor cells, achieving self-blockade. Simultaneously, the outer-membrane protein of LOMV recruits cytotoxic lymphocyte cells and natural killer cells to tumor tissues and stimulates them to secrete IFN-γ , improving the antitumor activity of the PD-1/PD-L1 self-blocking therapy.