Co-transfer of human wild-type p53 and granulocyte-macrophage colony-stimulating factor genes via recombinant adenovirus induces apoptosis and enhances immunogenicity in laryngeal cancer cells

Co-transfer of immunomodulatory and anti-proliferative genes may be the bas is for new strategies to enhance tumor regression. The purpose of this stud y was to develop a combination gene therapy strategy for the treatment of l aryngeal cancer. Human wild-type p53 and,granulocyte-macrophage colony-stim ulating factor (GM-CSF) genes were transferred into human laryngeal cancer cells mediated by adenovirus type 5 vector co-expressing human wild-type p5 3 and GM-CSF (Ad-p53/GM-CSF). By the introduction of the wild-type p53 gene , the growth of human laryngeal cancer Hep-2 cells was inhibited and their apoptosis was induced. By the introduction of the GM-CSF gene, the immunoge nicity of cancer cells was enhanced. Significant proliferation of tumor inf iltrating lymphocytes and tumor-specific cytotoxicity of cytotoxic T lympho cytes were induced by Ad-p53/GM-CSF-infected cancer cells in vitro. The res ults suggest that the co-transfer of human wild-type p53 and GM-CSF genes i nto tumor cells via recombinant adenovirus may be further developed into an effective and practical combination gene therapy strategy for laryngeal ca ncer. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.