https://scholars.lib.ntu.edu.tw/handle/123456789/567911
標題: | Electroporation-mediated IL-12 gene therapy in a transplantable canine cancer model | 作者: | Chuang T.-F. Lee S.-C. Liao K.-W. Hsiao Y.-W. Lo C.-H. BOR-LUEN CHIANG Lin X.-Z. Tao M.-H. Chu R.-M. |
關鍵字: | Canine transmissible venereal tumor; Electroporation; Gene therapy; IL-12; Intratumoral | 公開日期: | 2009 | 卷: | 125 | 期: | 3 | 起(迄)頁: | 698-707 | 來源出版物: | International Journal of Cancer | 摘要: | Interleukin-12 (IL-12) is effective in treating many types of rodent tumors, but has been unsuccessful in most human clinical trials, suggesting that animal models of more clinical relevance are required for evaluating human cancer immunotherapy. Herein, we report on the effectiveness of gene therapy with plasmid encoding human IL-12 (pIL-12) through in vivo electroporation in the treatment of beagles with a canine tumor, the canine transmissible venereal tumor (CTVT). The optimal electroporation conditions for gene transfer into CTVTs were tested by luciferase activity and determined to be a voltage of 200 V and duration of 50 msec, with the number of shocks set at 10 pulses, and the use of an electrode with 2 needles. Under these conditions, intratumoral administration of as little as 0.1 mg pIL-12 followed by electroporation significantly inhibited the growth of well-established tumors and eventually led to complete tumor regression. Furthermore, local pIL-12 treatment also induced a strong systemic effect that prevented new tumor growth and cured established tumors at distant locations. Intratumoral administration of pIL-12 greatly elevated the IL-12 level in the tumor masses, but produced only a trace amount in the serum. A high level of IFN-gamma mRNA was also detected in the treated tumor masses. pIL-12 gene therapy attracted significantly more lymphocytes infiltrating the tumors, including CD4+ and CD8+ T cells, and the surface expression of MHC I and MHC II molecules on CTVT cells was greatly increased after pIL-12 therapy. This treatment also induced apoptosis of the tumor cells as detected by Annexin V. More importantly, delivery of pIL-12 with intratumoral electroporation did not result in any detectable toxicity in the dogs. We conclude that intratumoral electroporation of the pIL-12 gene could cause profound immunologic host responses and efficiently treat CTVT in beagle dogs. The results also indicate that CTVT is an excellent large animal cancer model for testing immunogene therapies mediated by electroporation. ? 2009 UICC. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-67650065521&doi=10.1002%2fijc.24418&partnerID=40&md5=4312639a3afaad4a822b445d41f73135 https://scholars.lib.ntu.edu.tw/handle/123456789/567911 |
ISSN: | 0020-7136 | DOI: | 10.1002/ijc.24418 | SDG/關鍵字: | gamma interferon; interleukin 12; lipocortin 5; luciferase; major histocompatibility antigen class 1; major histocompatibility antigen class 2; messenger RNA; animal cell; animal experiment; animal model; animal tissue; animal venereal tumor; apoptosis; article; cancer immunotherapy; cancer model; canine transmissible venereal tumor; CD4+ T lymphocyte; CD8+ T lymphocyte; controlled study; dog; electrode; electroporation; gene delivery system; gene therapy; immune response; in vivo study; lymphocytic infiltration; nonhuman; priority journal; tumor cell; tumor growth; tumor localization; tumor regression; Animals; Apoptosis; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Disease Models, Animal; Dog Diseases; Dogs; Electrochemotherapy; Flow Cytometry; Gene Therapy; Genes, MHC Class I; Genes, MHC Class II; Immunotherapy; Interferon-gamma; Interleukin-12; Neoplasm Transplantation; Venereal Tumors, Veterinary |
顯示於: | 醫學系 |
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