病毒载体
遗传增强
全身给药
离体
转导(生物物理学)
造血
生物
外周血单个核细胞
CD8型
T细胞
基因传递
免疫疗法
细胞生物学
免疫学
癌症研究
干细胞
免疫系统
基因
体内
体外
重组DNA
遗传学
生物化学
作者
Qi Zhou,Katharina M. Uhlig,Anke Muth,Janine Kimpel,Camille Lévy,Robert C. Münch,Janna Seifried,Anett Pfeiffer,Alexandra Trkola,Cheick Coulibaly,Dorotheé von Laer,Winfried S. Wels,Udo F. Hartwig,Els Verhoeyen,Christian J. Buchholz
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2015-08-01
卷期号:195 (5): 2493-2501
被引量:54
标识
DOI:10.4049/jimmunol.1500956
摘要
Abstract Playing a central role in both innate and adaptive immunity, CD4+ T cells are a key target for genetic modifications in basic research and immunotherapy. In this article, we describe novel lentiviral vectors (CD4-LV) that have been rendered selective for human or simian CD4+ cells by surface engineering. When applied to PBMCs, CD4-LV transduced CD4+ but not CD4− cells. Notably, also unstimulated T cells were stably genetically modified. Upon systemic or intrasplenic administration into mice reconstituted with human PBMCs or hematopoietic stem cells, reporter gene expression was predominantly detected in lymphoid organs. Evaluation of GFP expression in organ-derived cells and blood by flow cytometry demonstrated exclusive gene transfer into CD4+ human lymphocytes. In bone marrow and spleen, memory T cells were preferentially hit. Toward therapeutic applications, we also show that CD4-LV can be used for HIV gene therapy, as well as for tumor therapy, by delivering chimeric Ag receptors. The potential for in vivo delivery of the FOXP3 gene was also demonstrated, making CD4-LV a powerful tool for inducible regulatory T cell generation. In summary, our work demonstrates the exclusive gene transfer into a T cell subset upon systemic vector administration opening an avenue toward novel strategies in immunotherapy.
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