Antisense Blocking of Interleukin-l? Converting Enzyme (ICE) Expression Inhibit Activation Induced Apoptosis of T Cell with Retroviral Vector / 中国肿瘤生物治疗杂志

ABSTRACT

Cytotoxic T lymphowcytes (CTL) play a major role in host anti-tumor immune responses. A major obstacle to the application of adoptive immunotherapy in the treatment of human maligancy is the inability to generate enough activated CTLs since the cytotoxic T cell undergoes activation induced apoptosis during destroying tumor cells. It is important to study how to limit activaton induced apoptosis of T cell so as to maximize the number of CTL and to enhance the tumor cytotoxicity. We have used CD3-induced Jurkat cell line as an activated T cell apoptosis model and introduced the anti-sense ICE cDNA into Jurkat T cells with retroviral vector. The effect on apoptosis of Jurkat cell induced by anti-CD3 or anti-Fas monoclonal antibody was evaluated after transfection with antisense human ICE. We found that the level of ICE expression in Jurkat cell transduced by the vector decreased and apoptosis was minimized in antisense ICE-transfected Jurkat cell after anti-CD3 or anti-Fas treatment. These results suggest that antisense blocking of ICE expression can partially inhibit Jurkat cell apoptosis induced by anti-CD3 or anti-Fas. Thus, applying antisense blocking of ICE to gene therapy may block the apoptosis of activated T cells, furthennore, enhance the antitumor effect.