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Cotransduction of CCL27 gene can improve the efficacy and safety of IL-12 gene therapy for cancer.
- Source :
- Gene Therapy; Mar2007, Vol. 14 Issue 6, p491-502, 12p, 6 Diagrams, 1 Chart
- Publication Year :
- 2007
-
Abstract
- Interleukin-12 (IL-12) is a potent antitumoral cytokine, but high doses are toxic. Herein, we demonstrate that combinational transduction of IL-12 and CC-chemokine ligand-27 (CCL27) genes into pre-existing murine OV-HM ovarian carcinoma and Meth-A fibrosarcoma, by using RGD fiber-mutant adenoviral vectors, could induce tumor regression and relieve systemic side effects more effectively than either treatment alone. The antitumor activity of the IL-12 and CCL27 combination treatment was T-cell-dependent, and development of long-term specific immunity was confirmed in rechallenge experiments. Immunohistochemical analysis of tumors transduced with CCL27 gene alone or cotransduced with IL-12 and CCL27 genes showed significant increases in numbers of infiltrating CD3<superscript>+</superscript> T cells, which included both CD4<superscript>+</superscript> and CD8<superscript>+</superscript> cells. Additionally, cotransduction with IL-12 and CCL27 genes could more efficiently activate tumor-infiltrating immune cells than transduction with CCL27 alone, as determined by the frequency of perforin-positive cells and expression levels of IFN-γ. Furthermore, mice treated with the IL-12 and CCL27 combination compared with those treated with IL-12 alone showed milder pathological changes, for example, lymphocyte infiltration and extramedullary hematopoiesis, in lung, liver and spleen. Our data provide evidence that combinational in vivo transduction with IL-12 and CCL27 genes is a promising approach for the development of cancer immunogene therapy that can simultaneously recruit and activate tumor-infiltrating immune cells.Gene Therapy (2007) 14, 491–502. doi:10.1038/sj.gt.3302892; published online 4 January 2007 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09697128
- Volume :
- 14
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 24245724
- Full Text :
- https://doi.org/10.1038/sj.gt.3302892