| Suppression of Tumor Formation and Induction of Natural Killer Cell Activity in BALB/c Nude Mice by Human B7-1 (CD80) Gene Transfer Subcutaneously Injected with Human Hepatocellular Carcinoma Cells (Huh-7) |
| Seung Kew Yoon, M.D., Tai Gyu Kim, M.D.1, Hyun Il Cho, M.D.1, Bong Soo Lee, M.D.,
Se Hyun Cho, M.D., Nam Ik Han, M.D., Young Sok Lee, M.D., Jeong Won Jang, M.D.,
Kyu Won Chung, M.D., Hee Sik Sun, M.D. and Boo Sung Kim, M.D. |
| Department of Internal Medicine, Department of Microbiology and Immunology1, College of Medicine,
The Catholic University of Korea, WHO Collaborating Center for Reference and Research on Viral Hepatitis,
Seoul, Korea |
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| ABSTRACT |
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Background/Aims
Immunogene therapy is extensively studied for a therapeutic modality of various cancers. This study was conducted to investigate the efficacy of immunogene therapy using the T-cell costimulatory molecule and human B7-1 (CD80, hB7-1) in an in vivo human hepatocellular carcinoma (HCC) model. Methods: The stable HCC cell line expressing hB7-1 gene was established using retroviral vector (Huh-7/hB7-1). Of fourteen BALB/c nude mice, 7 were subcutaneously injected with 2×106Huh-7/hB7-1 cells, while the other 7 were injected with 2×106Huh-7/mock cells as a control group. After the injection, the mice were observed weekly for three months for subcutaneous tumor formation. Assay for natural killer (NK) cell cytotoxicity and serum IFN-γ was performed at 1 and 2 weeks after inoculation. Results: In BALB/c nude mice inoculated with Huh-7/hB7-1 cells, no tumor growth was observed. BALB/c nude mice inoculated with Huh-7/hB7-1 cells showed significantly increased NK cell activities of splenocytes compared with those with Huh-7/mock cells. Serum IFN-γ was not measurable at 1 week, but significantly increased at 2 weeks after inoculation to the level of 470 pg/ml in BALB/c nude mice with Huh-7/mock cells and 521 pg/ml in BALB/c nude mice with Huh-7/hB7-1. Conclusions: Our results demonstrate the in vivo anti-tumor immunity and NK cell activation by transfer of hB7-1 gene into human HCC in xenogeneic BALB/c nude mice model. This approach may provide a tool for the development of immunogene therapies against human malignant tumors.(Korean J Hepatol 2003;9:124-134) |
| KeyWords:
B7-1 (CD80), Neoplasm/Liver/Hepatocellular carcinoma, NK cell, Nude mouse |
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