title: Adenovirus-mediated combined P16 gene and GM-CSF gene therapy for the treatment of established tumor and induction of antitumor immunity.
abstract: Antitumor effects of combined transfer of P16 and cytokine genes were investigated in this study. The adenovirus harboring the P16 gene (AdP16) and murine granulocyte-macrophage colony-stimulating factor gene (AdGM-CSF) were utilized for the treatment of established tumors. The mice were inoculated subcutaneously with Renca cells and, 6 days later, received an intratumoral injection of AdP16 in the presence or absence of AdGM-CSF. The results demonstrated that tumor-bearing mice treated with AdP16 in combination with AdGM-CSF showed more potent inhibition of tumor growth and survived much longer than did mice treated with AdP16, AdGM-CSF, adenovirus expressing beta-galactosidase, or phosphate-buffered saline alone (P<.01). The tumor mass showed obvious necrosis and inflammatory cell infiltration, and more CD(4)(+) and CD(8)(+) T cells infiltrating the tumor after combined therapy. After combined therapy, the expression of MHC-1 (H-2K(d)) and Fas molecules on freshly isolated tumor cells increased greatly. The activity of specific cytotoxic T lymphocytes was also found to be induced more significantly after the combined therapy (P<.01). Our results demonstrated that combined therapy with P16 and GM-CSF genes can inhibit the growth of established tumors in mice significantly and induce antitumor immunity of the host efficiently.
authors.affiliation: The Department of Urology, Changhai Hospital, The Second Military Medical University, Shanghai, China. wlhui@online.sh.cn
authors.forename: Linhui
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Qi
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Dianwen
authors.initials: D
authors.lastname: Ju
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000628:therapy; D003131:Combined Modality Therapy; D004274:DNA, Recombinant; D005260:Female; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D019942:Genes, p16; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006183:H-2 Antigens / Q000276:immunology; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007680:Kidney Neoplasms / Q000276:immunology* / Q000628:therapy; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
chemical_list: D004274:DNA, Recombinant; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D019014:fas Receptor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor