title: Fusion cytokine IL-2-GMCSF enhances anticancer immune responses through promoting cell-cell interactions.
abstract: BACKGROUND
  Potent antitumor responses can be induced through cytokine immunotherapy. Interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are among the most effective cytokines to induce tumor-specific systemic immune responses and can act synergistically. To overcome the limitations of combined use of these two cytokines, we have constructed an IL2-GMCSF fusion protein and characterized its antitumor effects in this study.
  
  
  METHODS
  The expression of IL-2 receptor and GM-CSF receptor of cell lines were detected with quantitative real-time PCR. On this basis, the bioactivities of IL2-GMCSF, especially effects on DC2.4 cells were assayed. Another function of IL2-GMCSF-bridge two types of cells-was assessed by cell contact counting and cytotoxicity assays. The anti-tumor activity in vivo of IL2-GMCSF was evaluated in the melanoma model. The statistical significance among treatment groups were determined by One-Way ANOVA.
  
  
  RESULTS
  The fusion protein IL2-GMCSF maintained the activities of IL-2 and GM-CSF, and could significantly promote DC2.4 cell activities, including phagocytosis, proliferation and cytokine secretion. In addition to the inherent cytokine activity, IL2-GMCSF bridges direct cell-cell interactions and enhances splenocyte killing efficacy against multiple tumor cell lines in vitro. Co-injection of IL2-GMCSF and inactivated B16F10 mouse melanoma cells induced complete immunoprotective responses in about 30 % of mice.
  
  
  CONCLUSIONS
  These results suggested that IL2-GMCSF can efficiently regulate immune responses against tumors. Furthermore, as the bridging effect relies on both IL-2R and GM-CSFR and promotes interactions between immune and tumor cells, IL2-GMCSF may be utilized as a useful tool for dissecting specific immune responses for future clinical applications.
authors: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, #1838, Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, Peoples' Republic of China. wencaoxi@163.com.
authors: Qian
authors: Q
authors: Wen
authors: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, #1838, Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, Peoples' Republic of China. 578718829@qq.com.
authors: Wenjing
authors: W
authors: Xiong
authors: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, #1838, Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, Peoples' Republic of China. 411487251@qq.com.
authors: Jianchun
authors: J
authors: He
authors: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, #1838, Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, Peoples' Republic of China. 2272196349@qq.com.
authors: Shimeng
authors: S
authors: Zhang
authors: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, #1838, Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, Peoples' Republic of China. 467587406@qq.com.
authors: Xialin
authors: X
authors: Du
authors: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, #1838, Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, Peoples' Republic of China. vanguard_1987@163.com.
authors: Sudong
authors: S
authors: Liu
authors: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, #1838, Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, Peoples' Republic of China. 190254050@qq.com.
authors: Juanjuan
authors: J
authors: Wang
authors: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, #1838, Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, Peoples' Republic of China. zmq12@163.com.
authors: Mingqian
authors: M
authors: Zhou
authors: Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, #1838, Northern Guangzhou Ave, Guangzhou, 510515, Guangdong, Peoples' Republic of China. maryhmz@126.com.
authors: Li
authors: L
authors: Ma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002450:Cell Communication / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D007109:Immunity / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor