Improvement of peptide-based tumor immunotherapy using pH-sensitive fusogenic polymer-modified liposomes

Yuta Yoshizaki, Eiji Yuba, Toshihiro Komatsu, Keiko Udaka, Atsushi Harada, Kenji Kono

研究成果: Article査読

27 被引用数 (Scopus)

抄録

To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and L-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG) and were loaded with antigenic peptides derived from ovalbumin (OVA) OVA-I (SIINFEKL), and OVA-II (PSISQAVHAAHAEINEAPβA), which bind, respectively, to major histocompatibility complex (MHC) class I and class II molecules on dendritic cell (DCs). The peptide-loaded liposomes were taken up efficiently by DCs. The peptides were delivered into their cytosol. Administration of OVA-I-loaded MGlu-HPG-modified liposomes to mice bearing OVA-expressing E.G7-OVA tumors induced the activation of OVA-specific CTLs much more efficiently than the administration of free OVA-I peptide did. Mice strongly rejected E.G7-OVA cells after immunization with OVA-I peptide-loaded MGlu-HPG liposomes, although mice treated with free OVA-I peptide only slightly rejected the cells. Furthermore, efficient suppression of tumor volume was observed when tumor-bearing mice were immunized with OVA-I-peptide-loaded liposomes. Immunization with OVA-II-loaded MGlu-HPG-modified liposomes exhibited much lower tumor-suppressive effects. Results indicate that MGlu-HPG liposomes might be useful for improvement of CTL-inducing peptides for efficient cancer immunotherapy.

本文言語English
論文番号1284
ジャーナルMolecules
21
10
DOI
出版ステータスPublished - 2016 10 1
外部発表はい

ASJC Scopus subject areas

  • 分析化学
  • 化学(その他)
  • 分子医療
  • 薬科学
  • 創薬
  • 物理化学および理論化学
  • 有機化学

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