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 basis for new strategies to enhance tumor regression. The purpose of this study was to develop a combination gene therapy strategy for the treatment of laryngeal cancer. Human wild-type p53 and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes were transferred into human laryngeal cancer cells mediated by adenovirus type 5 vector co-expressing human wild-type p53 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 immunogenicity of cancer cells was enhanced. Significant proliferation of tumor infiltrating lymphocytes and tumor-specific cytotoxicity of cytotoxic T lymphocytes were induced by Ad-p53/GM-CSF-infected cancer cells in vitro. The results suggest that the co-transfer of human wild-type p53 and GM-CSF genes into tumor cells via recombinant adenovirus may be further developed into an effective and practical combination gene therapy strategy for laryngeal cancer.
Qiu
Z
Z
Beijing Institute of Radiation Medicine, 27 Taiping Road, 100850, Beijing, PR China.
Lao
M
M
Wu
C
C
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D018014:Gene Transfer Techniques; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D007959:Lymphocyte Culture Test, Mixed; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D016159:Tumor Suppressor Protein p53; D016178:Granulocyte-Macrophage Colony-Stimulating Factor