1. Fusion cytokine IL-2-GMCSF enhances anticancer immune responses through promoting cell-cell interactions.
- Author
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Wen Q, Xiong W, He J, Zhang S, Du X, Liu S, Wang J, Zhou M, and Ma L
- Subjects
- Animals, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Cell Death drug effects, Cell Line, Tumor, Gene Expression Regulation, Neoplastic drug effects, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, Interleukin-2 pharmacology, Male, Melanoma genetics, Melanoma pathology, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor genetics, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor metabolism, Receptors, Interleukin-2 genetics, Receptors, Interleukin-2 metabolism, Recombinant Fusion Proteins pharmacology, Cell Communication drug effects, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Immunity drug effects, Interleukin-2 therapeutic use, Melanoma drug therapy, Melanoma immunology, Recombinant Fusion Proteins therapeutic use
- 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., Conclusion: 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.
- Published
- 2016
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