Levine Bruce L, Humeau Laurent M, Boyer Jean, MacGregor Rob-Roy, Rebello Tessio, Lu Xiaobin, Binder Gwendolyn K, Slepushkin Vladimir, Lemiale Franck, Mascola John R, Bushman Frederic D, Dropulic Boro, June Carl H
Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17372-7. doi: 10.1073/pnas.0608138103. Epub 2006 Nov 7.
We report findings from a clinical evaluation of lentiviral vectors in a phase I open-label nonrandomized clinical trial for HIV. This trial evaluated the safety of a conditionally replicating HIV-1-derived vector expressing an antisense gene against the HIV envelope. Five subjects with chronic HIV infection who had failed to respond to at least two antiviral regimens were enrolled. A single i.v. infusion of gene-modified autologous CD4 T cells was well tolerated in all patients. Viral loads were stable, and one subject exhibited a sustained decrease in viral load. CD4 counts remained steady or increased in four subjects, and sustained gene transfer was observed. Self-limiting mobilization of the vector was observed in four of five patients. There is no evidence for insertional mutagenesis after 21-36 months of observation. Immune function improved in four subjects. Lentiviral vectors appear promising for gene transfer to humans.
我们报告了在一项针对HIV的I期开放标签非随机临床试验中慢病毒载体的临床评估结果。该试验评估了一种表达针对HIV包膜反义基因的条件性复制HIV-1衍生载体的安全性。招募了5名对至少两种抗病毒方案无反应的慢性HIV感染患者。所有患者对单次静脉输注基因修饰的自体CD4 T细胞耐受性良好。病毒载量稳定，一名受试者的病毒载量持续下降。四名受试者的CD4计数保持稳定或增加，并观察到持续的基因转移。在五名患者中的四名观察到载体的自限性动员。经过21 - 36个月的观察，没有插入诱变的证据。四名受试者的免疫功能得到改善。慢病毒载体在基因转移到人体方面似乎很有前景。
