Thus, this study illustrates a potential gene therapy strategy for glioblastoma multiforme patients using GM-CSF and/or B7-2 transduced tumor vaccines. Furthermore, vaccination with irradiated GM-CSF/B7-2-transduced tumor cells markedly inhibited growth of wild-type tumors at distant sites. Growth suppression was greatest for B7-2. The tumor-killing efficiency of CAR-T cells was detected by ELISA and flow cytometry. GM-CSF- or B7-2-transduced tumors showed growth suppression in hu-PBL-recon-stituted mice compared to untransduced and/or unreconstituted controls. The effect of GM-CSF and/or B7-2 transducion on D54MG tumor growth in vivo was monitored in a novel allogeneic human peripheral blood lymphocyte–severe combined immunodeficiency mouse (Hu-PBL–SCID) model. Therapeutic gene expression by D54MG was high after transduction and selection (30 ng/10 6 cells/day for GM-CSF and >2 orders of magnitude fluorescence shift on flow cytometry for B7-2). We transduced the human glioblastoma cell line D54MG in vitro with genes encoding the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), the T cell co-stimulatory molecule B7-2, or both (in a bicistronic vector) via retroviral vectors. Its dismal prognosis has led to investigation of new treatment strategies such as immunogene therapy. Glioblastoma multiforme is the most common primary central nervous system neoplasm.
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