Antitumor effects obtained by autologous Lewis lung cancer cell vaccine engineered to secrete mouse interleukin 27 by means of cationic liposome.

Abstract

Interleukin-27 (IL-27), a novel IL-6/IL-12 family cytokine, plays an important role in the early regulation of Th1 responses. The cytokine IL-27 can exert a variety of immune-regulatory functions including cytotoxic T lymphocyte (CTL), CD4+, CD8+ T lymphocytes activation and interferon-γ (IFN-γ) production. In this study, we developed an effective and gene modified tumor cell vaccine. Lewis lung cancer cell LL/2 transfected with the DOTAP:cholesterol cationic liposome could express the mouse IL-27 (mIL-27) gene at a relative high level. The resultant transfectants were then irradiated with X-ray and used as a tumor cell vaccine. This tumor cell vaccine not only contained tumor associated antigen (TAA) of LL/2 cells but also secreted mIL-27 which could induce immune response in mice. The mice vaccinated with LL/2-mIL-27 performed strong tumor inhibiting effect accompanied with a high IFN-γ production. Both CD4+ and CD8+ T lymphocytes were significantly elevated in these mice vaccinated with LL/2-mIL-27 cell vaccine. Moreover, after depletion of CD4+, CD8+ T lymphocytes by injection of antibodies against CD4 and CD8, the vaccinated mice inoculated with autologous LL/2 cells were not protected from tumor challenge. In contrast, vaccinated mice inoculated with autologous LL/2 cells were treated with antibody against natural killer (NK)cells or normal rat IgG still possessed strong antitumor activity. Our data suggested that DOTAP:cholesterol cationic liposome was quite useful in generating an autologous tumor cell vaccine and mIL-27 could be therapeutically used to potentiate the host antitumor immunity.

• Authors: Junfeng Zhang, Hongwei Tian, Can Li, Lin Cheng, Shuang Zhang, Xiaomei Zhang, Ruibo Wang, Fen Xu, Lei Dai, Gang Shi, Xiaolei Chen, Yiming Li, Tao Du, Jie Deng, Yu Liu, Yang Yang, Yuquan Wei, Hongxin Deng
• Journal: Molecular immunology (Mol Immunol) Vol. 55 Issue 3-4 Pg. 264-74 (Oct 2013) ISSN: 1872-9142 [Electronic] England
• PMID: 23522926 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Cancer Vaccines
• Fatty Acids, Monounsaturated
• Il27 protein, mouse
• Interleukins
• Liposomes
• Quaternary Ammonium Compounds
• 1,2-dioleoyloxy-3-(trimethylammonium)propane

Topics

• Animals
• Cancer Vaccines (genetics, immunology, therapeutic use)
• Carcinoma, Lewis Lung (immunology, pathology, therapy)
• Cell Line, Tumor
• Fatty Acids, Monounsaturated
• Female
• Genetic Engineering (methods)
• Immunotherapy, Adoptive (methods)
• Interleukins (biosynthesis, genetics, metabolism)
• Liposomes
• Mice
• Mice, Inbred C57BL
• Quaternary Ammonium Compounds
• Rats
• T-Lymphocyte Subsets (immunology, pathology)
• Transfection