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Article

Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes

1
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan
2
Department of Immunology, School of Medicine, Kochi University, Kohasu, Okou-cho, Nankoku, Kochi 783-8505, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Chih-Chang Chu
Molecules 2016, 21(10), 1284; https://doi.org/10.3390/molecules21101284
Received: 15 July 2016 / Revised: 21 September 2016 / Accepted: 21 September 2016 / Published: 26 September 2016
(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)
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. View Full-Text
Keywords: peptide vaccine; pH-sensitive liposome; immunotherapy; dendritic cell; pH-sensitive polymer peptide vaccine; pH-sensitive liposome; immunotherapy; dendritic cell; pH-sensitive polymer
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MDPI and ACS Style

Yoshizaki, Y.; Yuba, E.; Komatsu, T.; Udaka, K.; Harada, A.; Kono, K. Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes. Molecules 2016, 21, 1284. https://doi.org/10.3390/molecules21101284

AMA Style

Yoshizaki Y, Yuba E, Komatsu T, Udaka K, Harada A, Kono K. Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes. Molecules. 2016; 21(10):1284. https://doi.org/10.3390/molecules21101284

Chicago/Turabian Style

Yoshizaki, Yuta, Eiji Yuba, Toshihiro Komatsu, Keiko Udaka, Atsushi Harada, and Kenji Kono. 2016. "Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes" Molecules 21, no. 10: 1284. https://doi.org/10.3390/molecules21101284

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