Growth suppression and immunogenicity enhancement of Hep-2 or primary laryngeal cancer cells by adenovirus-mediated co-transfer of human wild-type p53, granulocyte-macrophage colony-stimulating factor and B7-1 genes.
Co-transfer of immunomodulatory and antiproliferative genes may be the basis for new strategies to potentiate tumor regression. In this study, we evaluated the in vitro effect of the introduction of human wild-type p53, granulocyte-macrophage colony-stimulating factor (GM-CSF), and B7-1 genes via recombinant adenovirus on the growth and immunogenicity of Hep-2 or primary laryngeal cancer cells. By the introduction of wild-type p53 gene, the growth of Hep-2 cells was inhibited via enhanced apoptosis. By the introduction of GM-CSF and B7-1 genes, the immunogenicity of cancer cells was enhanced. Significant proliferation of tumor infiltrating lymphocytes (TILs) and tumor-specific cytotoxicity of cytotoxic T lymphocytes (CTLs) were induced in vitro. Furthermore, the combinative effect of GM-CSF and B7-1 was even more evident than that of any one of them singly. These results suggest that the co-transfer of human wild-type p53, GM-CSF and B7-1 genes into tumor cells via recombinant adenovirus may be further developed into a potential combination gene therapy strategy for cancer.
Qiu
Zhao-hua
ZH
Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, P.R. China.
Wu
Chu-tse
CT
Lao
Miao-fen
MF
Pan
Lu-zhe
LZ
Li
Yuan-min
YM
D000256:Adenoviridae; D017209:Apoptosis; D018122:B7-1 Antigen / Q000235:genetics*; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D016158:Genes, p53; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D049452:Green Fluorescent Proteins; D006801:Humans; D007668:Kidney; D007822:Laryngeal Neoplasms / Q000235:genetics / Q000473:pathology*; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D008164:Luminescent Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor