Dendritic cells with transduced survivin gene induce specific cytotoxic T lymphocytes in human urologic cancer cell lines.

摘要

OBJECTIVES: To investigate whether survivin-specific cytotoxic T lymphocytes (CTLs) could be induced by dendritic cells (DCs) transduced with survivin gene by adenoviral vector, and whether these CTLs would display cytotoxic activities against human urologic cancer cell lines. Survivin, a member of the inhibitor of apoptosis protein family, is expressed in most malignancies, but not in normal tissue. METHODS: Adenoviral vector encoding the human survivin gene was generated. Human DCs from healthy donors were transduced with human survivin gene by infection with adenoviral vector encoding the human survivin gene using the centrifugal method. Survivin-specific CTLs were induced from autologous peripheral blood mononuclear cells by DCs transduced with the survivin gene. The ability of CTLs to lyse cancer cell lines was assessed using the (51)Cr-release assay. RESULTS: DCs transduced with survivin gene could induce survivin-specific CTLs against various urologic malignancies such as bladder, kidney, and prostate cancer cells. This cytotoxic activity could be blocked by anti-CD8 and anti-major histocompatibility complex class I antibodies. We also found that this cytotoxic activity was specific for the survivin protein and human leukocyte antigen haplotype. CONCLUSIONS: DCs transduced with the survivin gene induced potent survivin-specific CTL responses in vitro. This suggests that cancer immunotherapy targets for survivin might offer a novel approach to treating various urologic cancers.