ANTIHIV INTERBODIES FOR GENE THERAPY IN CD4+ CELLS

病毒研究所（Virus Research Institute）和Dana Farber Cancer Institute 寻求支持临床前基因转移研究， 单核细胞，未感染和HIV-1的纯化CD 4 + T细胞 感染的个体将导致“细胞内免疫” 对抗HIV-1。研究建议将优化大规模 逆转录病毒基因转移细胞内单链抗体 HIV-1信封，进入临床环境所需的。 载体LNCs 105携带选择标记neoR和人neoR。 单链抗体F105。载体和包装细胞系已经被 制作。将基因转移到原代细胞中的最佳条件将 在来自HIV-1感染和未感染个体的细胞中建立。 在长期培养中检测HIV-1复制，以评估 抑制HIV-1患者细胞中的HIV-1复制， 将进行临床规模的CD 4 + T淋巴细胞转导。基因 转移、表达、细胞选择和扩增， 方案和细胞表面受体表达水平，形态学， 将评价细胞因子谱和对抗原刺激的应答。 DFCI“基因转移设施”和人员将参加这一预- 临床研究和未来的临床研究。

DESCRIPTION: Virus Research Institute and Dana Farber Cancer Institute seeks support for pre-clinical gene transfer studies utilizing peripheral mononuclear cells, purified CD4+ T-cells from uninfected and HIV-1 infected individuals that will result in "Intracellular immunization" against HIV-1. The research proposal will optimize large scale retroviral gene transfer of a intracellular single-chain antibody against the HIV-1 envelope, required for the proceeding into a clinical setting. The vector LNCs105 carries the selection marker neoR and the human single-chain antibody F105. Vectors and packaging cell lines have been produced. Optimal conditions for gene transfer into primary cells will be established in cells from HIV-1 infected and non-infected individuals. Testing HIV-1 replication in long term cultures to evaluate the ability to suppress HIV-1 replication in cells from HIV-1 patients and large clinical scale transduction of CD4+ T lymphocytes will be done. Gene transfer, expression, cell selection and expansion in "dry runs" of the protocol and the level of cell-surface receptor expression, morphology, cytokine profile, and response to antigen stimulation will be evaluated. DFCI "gene transfer facility" and personnel will participate in this pre- clinical arm and in future clinical proposals.