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Cationic Liposome/DNA Complexes Mediate Antitumor Immunotherapy by Promoting Immunogenic Tumor Cell Death and Dendritic Cell Activation
journal contribution
posted on 2020-06-12, 17:34 authored by Xiuxiu Cong, Huimin Tian, Shuhan Liu, Kuirong Mao, Hongmei Chen, Yanbao Xin, Feiqi Liu, Xin Wang, Xiandi Meng, Ge Zhu, Jialiang Wang, Xue Gao, Huizhu Tan, Yong-Guang Yang, Tianmeng SunImmunotherapy
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.
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Promoting Immunogenic Tumor Cell DeathDendritic Cell Activation Immunotherapyactivationtumor-draining lymph nodeT cell-dependent antitumortumor formationcancer immunotherapyDOTAPtumor-specific CD 8plasmid DNA-encapsulated cationic lipid nanoparticleCationiccytotoxic T lymphocytesresponse ratestumor growthantigenicitytumor cell deathCLNintratumoral injectiontumor cellsantitumor immunityDSPE-mPEG 2000immunotherapeutic modalitiesDCcytotoxic effectsliposomedendritic cells
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