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).
- Author:
Seung Kew YOON
1
;
Tai Gyu KIM
;
Hyun Il CHO
;
Bong Soo LEE
;
Se Hyun CHO
;
Nam Ik HAN
;
Young Sok LEE
;
Jeong Won JANG
;
Kyu Won CHUNG
;
Hee Sik SUN
;
Boo Sung KIM
Author Information
1. Department of Internal Medicine, College of Medicine, The Catholic University of Korea. kimtg@cmc.cuk.ac.kr
- Publication Type:Original Article ; English Abstract
- Keywords:
B7-1 (CD80);
Neoplasm/Liver/Hepatocellular carcinoma;
NK cell;
Nude mouse
- MeSH:
Animals;
Antigens, CD80/*genetics;
Cytotoxicity, Immunologic;
Gene Transfer Techniques;
Humans;
Interferon-gamma/metabolism;
Killer Cells, Natural/*immunology;
Liver Neoplasms, Experimental/genetics/*immunology;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Neoplasm Transplantation
- From:The Korean Journal of Hepatology
2003;9(2):124-134
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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 X 10(6) Huh-7/hB7-1 cells, while the other 7 were injected with 2 X 10(6) Huh-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-gamma 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-gamma 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.