Conference Paper

Anti- Esophageal Cancer Active Immunity Induced by FasL/B7-1 Genes Modified Tumor Cells

Dept. of Cardio-Thoracic Surg., First Affiliated Hosp. of Suzhou Univ., Suzhou
DOI: 10.1109/ICBBE.2008.103 Conference: Bioinformatics and Biomedical Engineering, 2008. ICBBE 2008. The 2nd International Conference on
Source: IEEE Xplore


To study the activation of CTLs against esophageal cancer cells induced by FasL/B7-1 (FB-11)genes modified tumor cells, and to explore whether co-expression of FasL and B7-1 in Eca-109 tumor cells could initiate an synergistic antitumor effect. FasL and B7-1 genes were transfected into human Eca-109 Eca-109 cancer cells with adenovirus vectors. The positive clones were selected by G418. FasL and B7-1 were detected by Flow cytometry and RT-PCR . The abdominal infiltrating lymphocytes and sensitized spleen cells were obtained from the mice who were immunized with Eca-109/FB-11 or wild type Eca-109 cells intraperitoneally, and the cytotoxicity of these CTLs against tumor cells was determined by MTT assay. Flow cytometry and RT-PCR showed that FasL and B7-1 were highly expressed. FasL+/B7-1+ Eca-109 cells (Eca-109/FB-11) were inoculated subcutaneously in the dorsal skin of C57BL/6 mice and then they decreased their tumorigenicity greatly (z=2.15-46.10, p<0.01). The Eca-109/FB-11 cell-sensitized mice obtained the protective immune activity against the rechallenge of wild type Eca-109 cells (z=2.06-44.30, p<0.05). It was showed that the cytotoxicity of CTLs induced by Eca-109/FB-11 cells against Eca-109 was significantly higher than that of CTLs activated by wild-type Eca-109 cells (84.1plusmn2.4% vs 30.5plusmn2.3%, p<0.05). The results suggest that the FasL and B7-1 can effectively promote the activity of CTLs against esophageal cancer cells.

8 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: To further investigate the immunological mechanisms involved in Takayasu’s arteritis, we analyzed the T-cell receptor (TCR) Vγ and Vδ gene usage by infiltrating γδ T-cells and the expression of costimulatory molecules B7-1, B7-2, CD40, CD27 ligand (CD27L), CD30L, OX40L in the arterial tissue of a patient with Takayasu’s arteritis. We found that the repertoires of TCR Vγ as well as Vδ gene transcripts of the infiltrating cells were restricted as compared with those of peripheral blood lymphocytes from a patient with Takayasu’s arteritis. This strongly suggests that γδ T-cells as well as αβ T-cells, as we previously reported, were specifically involved in the pathogenesis of Takayasu’s arteritis. We also found that B7-1, B7-2, CD40, CD27L, CD30L, and OX40L were expressed in the arterial tissue, suggesting the roles for these costimulatory molecules in T-cell-mediated vascular injury in Takayasu’s arteritis. Our findings strongly support the involvement of T-cell-mediated immunological mechanisms in the pathogenesis of Takayasu’s arteritis.
    International Journal of Cardiology 08/2000; 75. DOI:10.1016/S0167-5273(00)00194-7 · 4.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Activation of T cells requires at least two signals: signal 1, via the T-cell receptor, and signal 2, in which a costimulatory molecule on the antigen presenting cell (APC) interacts with a ligand on the T cell. Dendritic cells (DCs) are the most potent APCs in part due to their expression of costimulatory molecules. DCs, however, constitute only a minor percentage of APCs in the body, and the in vitro preparation of DCs is both costly and time consuming. The studies reported here demonstrate that one can utilize other APCs, such as bone marrow progenitor cells (BMPCs) and make them markedly more effective as APCs; this was accomplished by their infection with recombinant poxviruses (either the replication-defective avipox or vaccinia), which contain transgenes for a triad of costimulatory molecules (B7-1, ICAM-1 and LFA-3, designated TRICOM). APCs infected with TRICOM vectors are shown to significantly enhance the activation of both naive and effector CD4(+) and CD8(+) T-cell populations. The use of TRICOM vectors in vaccine strategies is discussed.
    Critical Reviews in Oncology/Hematology 08/2001; 39(1-2):43-57. DOI:10.1016/S1040-8428(01)00123-8 · 4.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Since the rhesus is often used as a "gatekeeper" model for the evaluation of malaria and simian immunodeficiency virus (SIV)/HIV vaccines, the identification of strategies to enhance the activation of rhesus T cells would potentially aid in the generation of more potent vaccines directed against these infectious agents. Several molecules normally found on the surface of professional human APCs are capable of providing the second signals critical for T cell activation: B7-1 (CD80), ICAM-1 (CD54), and LFA-3 (CD58). With the exception of B7, T cell costimulatory molecules in the rhesus have not been identified. We have recently designed and characterized both recombinant vaccinia and recombinant avipox vectors containing the transgenes for a triad of human T cell costimulatory molecules (B7-1, ICAM-1, LFA-3; designated TRICOM). Here, we demonstrate the enhanced activation of rhesus T cells stimulated with rhesus APCs infected with TRICOM vectors in the presence of signal 1. Infection with TRICOM vectors led to significant improvement of APC capabilities in terms of reduction of the amount of signal 1 needed to activate naive T cells, and reduction in the amount of APCs required to activate T cells using a constant amount of signal 1. Antibody blocking studies demonstrated that each of the three costimulatory molecule transgenes contributed to the enhanced proliferation of T cells. TRICOM-enhanced T cell activation was shown to correspond to increases in type 1 cytokines and a reduced level of apoptosis. TRICOM-infected autologous B cells from rhesus immunized with either an SIV vaccine or a malaria vaccine stimulated significantly greater levels of IFN-gamma in response to specific peptide than stimulation with uninfected autologous B cells or B cells infected with wild-type vector. The ability to augment immune responses using poxvirus-based vaccines containing multiple costimulatory molecule transgenes can now be addressed in the rhesus macaque model.
    Vaccine 01/2002; 20(5-6):744-55. DOI:10.1016/S0264-410X(01)00409-1 · 3.62 Impact Factor