Antitumor effects obtained by autologous Lewis lung cancer cell vaccine engineered to secrete mouse Interleukin 27 by means of cationic liposome.
Zhang, Junfeng a,1; Tian, Hongwei a,1; Li, Can a; Cheng, Lin a; Zhang, Shuang a; Zhang, Xiaomei a; Wang, Ruibo a; Xu, Fen a; Dai, Lei a; Shi, Gang a; Chen, Xiaolei a; Li, Yiming a; Du, Tao a; Deng, Jie a; Liu, Yu a; Yang, Yang a; Wei, Yuquan a; Deng, Hongxin a,b,*
[Article]
Molecular Immunology.
55(3-4):264-274, October 2013.
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: 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-[gamma] (IFN-[gamma]) 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-[gamma] 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.
(C) 2013Elsevier, Inc.