[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)].
OBJECTIVE
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.
Yoon
Seung Kew
SK
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Kim
Tai Gyu
TG
Cho
Hyun Il
HI
Lee
Bong Soo
BS
Cho
Se Hyun
SH
Han
Nam Ik
NI
Lee
Young Sok
YS
Jang
Jeong Won
JW
Chung
Kyu Won
KW
Sun
Hee Sik
HS
Kim
Boo Sung
BS
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics*; D003602:Cytotoxicity, Immunologic; D018014:Gene Transfer Techniques; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation
D018122:B7-1 Antigen; D007371:Interferon-gamma