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Inhibition of colon tumor growth by IL-15 immunogene therapy
Xianghui He1, Weidong Li, Yifeng Wang
1Department of General Surgery, Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin 300052, PR China. humphreyhe@163.com
Abstract:
Interleukin-15 is a pleiotropic cytokine that has potential for cancer immunegene therapy. We previously reported the construction and characterization of IL-15 overexpression vectors pHi2-IL15-CMV-tat (L1) and pHi2-spIL15-CMV-tat (L3), as well as carcinoembryonic antigen promoter-amplified IL-15 expression plasmid vectors pHi2-IL15-CEA-tat (L2) and pHi2-spIL15-CEA-tat (L4). In the current study, we evaluated the expression and therapeutic efficacy of these vectors using a mouse colon carcinoma model. Plasmid vectors were transfected into SW480 and MCF-7 cells, and IL-15 overexpression was confirmed. IL-15 expressed by transfected tumor cells stimulated spleen cell proliferation in vitro. Intraperitoneal injection of plasmid pHi2-spIL15-CMV-tat (L3) into mice resulted in transgene expression by peritoneal mesothelial cells, inhibited CT-26 tumor growth and prolonged the survival of tumor-bearing mice. In addition, the in vivo transfection of plasmid pHi2-spIL15-CMV-tat (L3) via electroporation slowed the tumor formation of subcutaneously inoculated CT-26 cells. These data suggest that IL-15 overexpression achieves therapeutic effects in a mouse cancer model and that these gene transfer approaches should be further evaluated for use in the treatment of human cancers.
Insights
Interleukin-15 (IL-15) gene therapy shows promise for cancer treatment. Overexpressing IL-15 in a mouse colon cancer model inhibited tumor growth and improved survival, suggesting potential for human cancer therapy.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Interleukin-15 (IL-15) is a cytokine with potential in cancer immunotherapy.
- Previous work established IL-15 overexpression vectors, including plasmid vectors amplified by the carcinoembryonic antigen promoter.
Purpose of the Study:
- To evaluate the expression and therapeutic efficacy of IL-15 overexpression vectors in a mouse colon carcinoma model.
- To assess the potential of gene transfer approaches for cancer treatment.
Main Methods:
- Transfection of plasmid vectors into SW480 and MCF-7 cells to confirm IL-15 overexpression.
- In vitro assessment of spleen cell proliferation stimulated by IL-15 from transfected tumor cells.
- In vivo studies involving intraperitoneal injection and electroporation of IL-15 plasmid vectors in mice bearing CT-26 tumors.
Main Results:
- IL-15 overexpression was confirmed in transfected cells.
- Transfected tumor cells expressing IL-15 stimulated spleen cell proliferation in vitro.
- Intraperitoneal injection of pHi2-spIL15-CMV-tat (L3) inhibited CT-26 tumor growth and prolonged survival.
- In vivo electroporation of pHi2-spIL15-CMV-tat (L3) slowed tumor formation in a subcutaneous mouse model.
Conclusions:
- IL-15 overexpression demonstrates therapeutic effects in a preclinical mouse cancer model.
- Gene transfer strategies utilizing IL-15 hold promise for future human cancer therapies.
- Further evaluation of these gene transfer approaches is warranted for clinical application.
