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Fusion cytokine IL-2-GMCSF enhances anticancer immune responses through promoting cell-cell interactions.
- Source :
-
Journal of Translational Medicine . 2/5/2016, Vol. 14, p1-13. 13p. - Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *INTERLEUKIN-2
*CELL communication
*ANTINEOPLASTIC agents
*IMMUNOTHERAPY
*GRANULOCYTE-macrophage colony-stimulating factor
*CHIMERIC proteins
*PHAGOCYTOSIS
*ANIMAL experimentation
*CELL death
*CELL lines
*CELL receptors
*GENES
*IMMUNITY
*MELANOMA
*MICE
*RECOMBINANT proteins
*PHARMACODYNAMICS
*THERAPEUTICS
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 14
- Database :
- Academic Search Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 112816610
- Full Text :
- https://doi.org/10.1186/s12967-016-0799-7