Cationic Liposome/DNA Complexes Mediate Antitumor Immunotherapy by Promoting Immunogenic Tumor Cell Death and Dendritic Cell Activation

Abstract

Immunotherapy has been successfully used in the treatment of multiple malignancies, but clinical studies revealed low response rates. Thus, the development of new effective immunotherapeutic modalities is urgently needed. Successfully inducing tumor cell death with enhanced antigenicity is important for the expansion and differentiation of tumor-specific CD8+ cytotoxic T lymphocytes. Cationic liposome/DNA complexes (CLN/DNA), which usually have obvious cytotoxic effects, may improve the antitumor immunity through enhancing the immunogenicity of dying tumor cells. Herein, we report that a plasmid DNA-encapsulated cationic lipid nanoparticle formulated with cholesterol, DOTAP, and DSPE-mPEG2000 significantly increases the tumor cell death with high antigenicity in vitro. Furthermore, the cationic liposome/DNA complex (CLN/DNA) treatment promotes the activation of dendritic cells (DCs). We also find that the intratumorally injected CLN/DNA successfully promoted the activation of DCs in the tumor-draining lymph node. Importantly, both local tumor growth and distant tumor formation were significantly inhibited by T cell-dependent antitumor immune responses after intratumoral injection of CLN/DNA. This study presents a simple and effective strategy for improving the cancer immunotherapy.