A novel liposomal recombinant lipoimmunogen enhances anti-tumor immunity

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• 作者：Kuan-Yin Shen^a ; Hsin-Yu Liu^a ; Hui-Ju Li^a ; Chiao-Chieh Wu^a ; Gunn-Guang Liou^b ; Yuan-Chih Chang^b ; Chih-Hsiang Leng^a ; ^c ; ^{leoleng@nhri.org.tw" class="auth_mail" title="E-mail the corresponding author} ; Shih-Jen Liu^a ; ^c ; ^{levent@nhri.org.tw" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DOPC ; 1 ; 2-dioleoyl-sn-glycero-3-phosphocholine ; DOTAP ; 1 ; 2-dioleoyl-3-trimethylammonium-propane (chloride salt) ; PG ; 1 ; 2-dioleoyl-sn-glycero-3-phospho-(1&prime ; -rac-glycerol) (sodium salt)
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 July 2016
• 年：2016
• 卷：233
• 期：Complete
• 页码：57-63
• 全文大小：943 K

文摘

Synthetic liposomes provide a biocompatible and biodegradable approach for delivering drugs and antigens. In addition, self-adjuvanting recombinant lipoproteins (rlipoproteins) can enhance Th1 anti-tumor immune responses via the TLR2 signaling pathway. To generate a liposomal rlipoprotein for a cancer immunotherapeutic vaccine, we assessed 3 types of synthetic liposomes for use with the rlipoproteins rlipoE7m and rlipoOVA. We determined that the cationic liposome DOTAP could stabilize anionic rlipoproteins and delay rlipoprotein release. Surprisingly, rlipoproteins and DOTAP could synergistically up-regulate CD83 expression in bone marrow-derived dendritic cells (BMDCs). Compared with other liposome formulations, the rlipoprotein/DOTAP formulation elicited higher cytotoxic T-lymphocyte (CTL) responses. To explore the mechanism of BMDC activation by rlipoprotein/DOTAP, we assessed the production of reactive oxygen species (ROS) and the TNF-α secretion of BMDCs. We observed that rlipoprotein/DOTAP induced ROS to the same extent as DOTAP did. In addition, TLR2 signaling was also required for the TNF-α secretion of rlipoprotein/DOTAP-treated BMDCs. Moreover, compared with rlipoOVA-treated BMDCs, rlipoOVA/DOTAP-treated BMDCs increased the levels of IFN-γ produced by OVA-specific T cells. We also observed that rlipoE7m/DOTAP treatment but not rlipoE7m treatment delayed tumor growth. These results indicate that the rlipoprotein/DOTAP formulation can synergistically activate BMDCs via ROS and the TLR2 signaling pathway. In summary, rlipoprotein/DOTAP is a novel and stable formulation for cancer immunotherapy.