Effects of immunotherapy of IL-6 and IL-15 plasmids on transmissible venereal tumor in beagles.

Abstract

Canine transmissible venereal tumor (CTVT) is a tumor with low MHC antigen expression and is an ideal tumor model for studying the interactions between host immunity and cancer cells. CTVTs produce high concentrations of TGF-beta to hamper the host immune responses and facilitate their growth progression. However, during the later stages of tumor progression, tumor-infiltrating lymphocytes secrete IL-6. This cytokine antagonizes TGF-beta and restores the IFN-gamma activities in promoting MHC antigen expression, and the NK cytotoxicity that has been repressed by TGF-beta is also activated. In this study, we applied combinatory treatment of IL-6 plasmid and IL-15 plasmid (pIL-6/pIL-15) to CTVT-bearing beagles. IL-6 was used as an anti-TGF-beta cytokine; IL-15 was used to promote NK- and CTVT-specific cytotoxicity. After intratumoral pIL-6/pIL-15 delivery mediated by electroporation, MHC antigen expression on CTVT cells was dramatically increased from in less than 5.9% to up to 34% of the tumor cells. The proportion of CD8(+) T cells infiltrating the tumor was also significantly elevated from 6.96+/-0.23% to 21.63+/-5.40%. In addition, the tumor-specific cytotoxicity was enhanced along with a marked increase in tumor-specific IFN-gamma-producing cells. These immune responses are believed to be the important forces driving the tumor towards regression. The results indicate that pIL-6/pIL-15 combinatory immunotherapy may facilitate a promising and effective means of treating tumors.

• Authors: Pei-Chung Chou, Tien-Fu Chuang, Tong-Rong Jan, Hsin-Chan Gion, Yi-Chun Huang, Han-Jon Lei, Win-Yin Chen, Rea-Min Chu
• Journal: Veterinary immunology and immunopathology (Vet Immunol Immunopathol) Vol. 130 Issue 1-2 Pg. 25-34 (Jul 15 2009) ISSN: 1873-2534 [Electronic] Netherlands
• PMID: 19200609 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Histocompatibility Antigens
• Interleukin-15
• Interleukin-6
• Transforming Growth Factor beta
• Interferon-gamma

Topics

• Animals
• Cell Line
• Cytotoxicity, Immunologic (immunology)
• Dog Diseases (immunology, therapy)
• Dogs
• Enzyme-Linked Immunosorbent Assay (veterinary)
• Flow Cytometry (veterinary)
• Histocompatibility Antigens (immunology)
• Humans
• Immunotherapy (methods, veterinary)
• Interferon-gamma (immunology)
• Interleukin-15 (blood, genetics, immunology)
• Interleukin-6 (blood, genetics, immunology)
• Killer Cells, Natural (immunology)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Plasmids (genetics)
• Transfection
• Transforming Growth Factor beta (antagonists & inhibitors, immunology)
• Venereal Tumors, Veterinary (immunology, therapy)