Exosome-based tumor antigens-adjuvant co-delivery utilizing genetically engineered tumor cell-derived exosomes with immunostimulatory CpG DNA

被引：312

作者：

Morishita, Masaki ^{[1
]}

Takahashi, Yuki ^{[1
]}

Matsumoto, Akihiro ^{[1
]}

Nishikawa, Makiya ^{[1
]}

Takakura, Yoshinobu ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut & Drug Metab, Sakyo Ku, Kyoto 6068501, Japan

来源：

BIOMATERIALS | 2016年 / 111卷

关键词：

Exosomes; Genetic engineering; Tumor antigens; CpG DNA; Cancer vaccine; Drug delivery; DENDRITIC CELLS; B16BL6-DERIVED EXOSOMES; IMMUNE-RESPONSES; CLINICAL-TRIALS; ANTITUMOR; STREPTAVIDIN; INDUCTION; INJECTION; SIRNA; CTL;

D O I：

10.1016/j.biomaterials.2016.09.031

中图分类号：

R318 [生物医学工程];

学科分类号：

100103 [病原生物学];

摘要：

For cancer immunotherapy via tumor antigen vaccination in combination with an adjuvant, major challenges include the identification of a particular tumor antigen and efficient delivery of the antigen as well as adjuvant to antigen-presenting cells. In this study, we proposed an efficient exosome-based tumor antigens-adjuvant co-delivery system using genetically engineered tumor cell-derived exosomes containing endogenous tumor antigens and immunostimulatory CpG DNA. Murine melanoma B16BL6 cells were transfected with a plasmid vector encoding a fusion streptavidin (SAV; a protein that binds to biotin with high affinity)-lactadherin (LA; an exosome-tropic protein) protein, yielding genetically engineered SAV-LA-expressing exosomes (SAV-exo). SAV-exo were combined with biotinylated CpG DNA to prepare CpG DNA-modified exosomes (CpG-SAV-exo). Fluorescent microscopic observation revealed the successful modification of exosomes with CpG DNA by SAV-biotin interaction. CpG-SAV-exo showed efficient and simultaneous delivery of exosomes with CpG DNA to murine dendritic DC2.4 cells in culture. Treatment with CpG-SAV-exo effectively activated DC2.4 cells and enhanced tumor antigen presentation capacity. Immunization with CpG-SAV-exo exhibited stronger in vivo antitumor effects in B16BL6 tumor-bearing mice than simple co-administration of exosomes and CpG DNA. Thus, genetically engineered CpG-SAV-exo is an effective exosome-based tumor antigens-adjuvant co-delivery system that will be useful for cancer immunotherapy. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：55 / 65

页数：11

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