Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified LiposomesReportar como inadecuado


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


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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

Abstract 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 polyglycidol 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





Autor: Yuta Yoshizaki 1, Eiji Yuba 1, Toshihiro Komatsu 2, Keiko Udaka 2, Atsushi Harada 1 and Kenji Kono 1,*

Fuente: http://mdpi.com/



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