Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response.

Abstract

Interleukin 23 (IL-23) is a member of the IL-12 family of heterodimeric cytokines, composed of p19 and p40 subunits, which exhibits immunostimulatory properties similar to IL-12. IL-23 has been shown to possess potent antitumor activities in several establishment models of cancer and a few therapeutic models, but the efficacy of local, adenoviral-mediated expression of IL-23 in established tumors has yet to be investigated. Here we have examined the antitumor activity of adenovirally delivered IL-23 in a day-7 MCA205 murine fibrosarcoma tumor model. Three intratumoral injections of adenovirus expressing IL-23 (Ad.IL-23) significantly increased animal survival and resulted in complete rejection of 40% of tumors, with subsequent generation of protective immunity and MCA205-specific cytotoxic T lymphocytes. In addition, we have shown that the antitumor activity of IL-23 is independent of IL-17, perforin and Fas ligand, but dependent on interferon-gamma, CD4(+) and CD8(+) T cells. These results demonstrate that direct intratumoral injection of adenovirus expressing IL-23 results in enhanced survival, tumor eradication and generation of protective immunity by generation of a Th1-type immune response.

• Authors: J Reay, S-H Kim, E Lockhart, J Kolls, P D Robbins
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 16 Issue 10 Pg. 776-85 (Oct 2009) ISSN: 1476-5500 [Electronic] England
• PMID: 19390568 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Fas Ligand Protein
• Interleukin-17
• Interleukin-23
• Perforin
• Interferon-gamma

Topics

• Adenoviridae (genetics)
• Animals
• CD4-Positive T-Lymphocytes (immunology)
• Cell Line, Tumor
• Fas Ligand Protein (immunology)
• Female
• Fibrosarcoma (genetics, immunology, therapy, virology)
• Gene Transfer Techniques
• Genetic Therapy (methods)
• Interferon-gamma (immunology)
• Interleukin-17 (biosynthesis)
• Interleukin-23 (biosynthesis, genetics, immunology)
• Kaplan-Meier Estimate
• Mice
• Mice, Inbred C57BL
• Perforin (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Transduction, Genetic