Effect Of Biological Characteristics Of Hepatoblastoma By Transduction Of Adenovirus-mediated Human B7-1 Gene

Background and ObjectThe immune response towards tumors is mainly mediated active T cells. T cell activation requires double signals. One way is via interaction of TCR with specific Ag on MHC molecules and the other way is via co-stimulatory molecules binding with their respective receptors on the T cells. In the absence of latter, it will induce apoptosis in T cells and consequently an immune evasion of tumor cells. Most co-stimulatory molecules are adhesion molecules. B7-1 is one of the important adhesion molecules.Hepatoblastoma is believed to be a poorly immunogenic malignant tumor. Ligands expressed on the tumor, which are mainly co-stimulatory molecules B7-1(CD80) and B7-2 (CD86) are not enough to bind on T cells. The lack of B7-1 is the main reason in the fail to induce an effective anti-tumor immune response. We tried to establish a hepatoblastoma cell line that strongly expressed B7-1 by transfering with human B7-1 gene and that investigated the effect of B7-1 expression on the induction of lymphocytes against hepatoblastoma and subsequent biological effect.MethodAfter retro viral transduction was applied in transfection hB7-1 into cell line, we investigated the expression of B7-1 by flow cytometric (FCM) analysis. Growth curves were determined and lymphocyte proliferation was evaluated by mixed lymphocyte culturing. ResultFCM revealed that HepG₂ cells expressed B7-1 on the cell surface but the expression level of B7-1 was very low (positive rate: 1.1%). While after retroviral transfection with hB7-l, the expression of B7-1 was very strong (positive rate: 18.5%) which is more than 16.8 times. After transfect ion with B7-1 gene, tumor cellproliferation was lagged and proliferation of lymphocytes was stimulated vigorously.ConclusionThe low expression of B7-1 is the main reason why hepG2 is poorly immunogenic. After transfection of B7-1 gene, B7-1 high expression positive clone in HepG2 cell is established. And transfection with B7-1 gene can inhibit the proliferation of hepG2 cell and stimulate vigorous proliferation of lymphocytes in vitro.