title: Recombinant adenoviral vector expressing human wild-type p53, GM-CSF, and B7-1 genes suppresses the growth of glioma in vivo.
abstract: Malignant gliomas are the most common of primary brain tumors and have been proven incurable with conventional treatments. Evidence have shown that a recombinant adenoviral vector expressing human wild-type p53, granulocyte-macrophage colony-stimulating factor (GM-CSF), and B7-1 genes (BB-102) may have antitumor effects in vitro. In this study, we investigated the effects of BB-102-based vaccine on glioma in vivo. An animal model using nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with human immune system was established. The mice were vaccinated with inactivated U251 glioma cells transduced with BB-102 or adenoviral vector expressing green fluorescence protein (Ad-GFP) as a control and followed by the challenge of live U251 glioma cells. Tumor growth and antitumor responses were measured. Data showed that mice vaccinated with BB-102 had significantly reduced local tumor growth compared to mice with Ad-GFP vaccination or the control group. Histopathological analysis displayed low tumor cell density and significant infiltration of human peripheral blood lymphocytes (HuPBLs) in the tumor tissues of mice transduced with BB-102. Immunohistochemical analysis showed that mutant p53 was not expressed in tumor tissues of mice with BB-102 vaccination, and the expression level of Ki67 was significantly lower in the tumor tissues of the BB-102 group than those in the Ad-GFP group or the control group. Further study demonstrated that mice with BB-102 vaccination had significantly increased total T cell numbers, total T cell proportion, CD4+ T cell proportion, and CD8+ T cell proportion in spleens, as well as higher value of IgG, IgA, and IgE in sera. These data suggest that the recombinant adenoviral vector expressing human wild-type p53, GM-CSF, and B7-1 genes could suppress glioma in NOD/SCID mice model and might be considered as a novel strategy for glioma therapy.
authors.affiliation: Department of Neurosurgery, General Hospital of Shenyang Military Area Command of Chinese PLA, 83 Wenhua Road, Shenyang, Liaoning, 110016, China.
authors.forename: Sizhe
authors.initials: S
authors.lastname: Feng
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Pan
authors.forename: Mingpei
authors.initials: M
authors.lastname: Liu
authors.forename: Xinli
authors.initials: X
authors.lastname: Feng
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Wei
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics*; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D016158:Genes, p53; D015316:Genetic Therapy; D005822:Genetic Vectors; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D014611:Vaccination
chemical_list: D018122:B7-1 Antigen; D007136:Immunoglobulins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor