title: Activation of cellular immunity and marked inhibition of liver cancer in a mouse model following gene therapy and tumor expression of GM-SCF, IL-21, and Rae-1.
abstract: BACKGROUND
  Cancer is both a systemic and a genetic disease. The pathogenesis of cancer might be related to dampened immunity. Host immunity recognizes nascent malignant cells - a process referred to as immune surveillance. Augmenting immune surveillance and suppressing immune escape are crucial in tumor immunotherapy.
  
  
  METHODS
  A recombinant plasmid capable of co-expressing granulocyte-macrophage colony- stimulating factor (GM-SCF), interleukin-21 (IL-21), and retinoic acid early transcription factor-1 (Rae-1) was constructed, and its effects determined in a mouse model of subcutaneous liver cancer. Serum specimens were assayed for IL-2 and INF-γ by ELISA. Liver cancer specimens were isolated for Rae-1 expression by RT-PCR and Western blot, and splenocytes were analyzed by flow cytometry.
  
  
  RESULTS
  The recombinant plasmid inhibited the growth of liver cancer and prolonged survival of tumor-loaded mice. Activation of host immunity might have contributed to this effect by promoting increased numbers and cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) following expression of GM-SCF, IL-21, and Rae-1. By contrast, the frequency of regulatory T cells was decreased, Consequently, activated CTL and NK cells enhanced their secretion of INF-γ, which promoted cytotoxicity of NK cells and CTL. Moreover, active CTL showed dramatic secretion of IL-2, which stimulates CTL. The recombinant expression plasmid also augmented Rae-1 expression by liver cancer cells. Rae-1 receptor expressing CTL and NK cells removed liver cancer.
  
  
  CONCLUSIONS
  The recombinant expression plasmid inhibited liver cancer by a mechanism that involved activation of cell-mediated immunity and Rae-1 in liver cancer.
authors.affiliation: Department of General Surgery, Pudong New Area District Zhoupu Hospital, Shanghai 201318, China. cmrlq@126.com.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Cheng
authors.forename: Kangkang
authors.initials: K
authors.lastname: Zhi
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Gao
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Li
authors.forename: Jiang
authors.initials: J
authors.lastname: Han
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015316:Genetic Therapy; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D034521:Nuclear Matrix-Associated Proteins / Q000096:biosynthesis / Q000235:genetics*; D029543:Nucleocytoplasmic Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D007376:Interleukin-2; D007378:Interleukins; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; C490521:Rae1 protein, mouse; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000098546:Interleukin-21