Diaz R M, Bateman A, Emiliusen L, Fielding A, Trono D, Russell S J, Vile R G
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota, USA.
Gene Ther. 2000 Oct;7(19):1656-63. doi: 10.1038/sj.gt.3301277.
The gibbon ape leukaemia virus envelope fusogenic membrane glycoprotein (GALV FMG) is a highly potent cytotoxic gene with great potential for use in cancer gene therapy. Here, we show that production of a VSV-G pseudotyped lentiviral vector expressing GALV FMG reconciles the requirements of viral production with the cytotoxic effects of GALV in human cells and has high titres on both dividing and quiescent tumour cells. Direct intratumoral injection of these stocks eradicated progressively growing human tumour xenografts. The potent bystander effect of the FMG transgene is a major contributor to the success of this approach but immunological activation may also be a factor. To our knowledge, this is the first demonstration in vivo of the potential both of FMG and lentiviral vectors for cancer gene therapy and highlights the importance of exploring different vector systems to complement the biological properties of the therapeutic transgene.
长臂猿白血病病毒包膜融合膜糖蛋白（GALV FMG）是一种高效的细胞毒性基因，在癌症基因治疗中具有巨大的应用潜力。在此，我们表明，表达GALV FMG的VSV-G假型慢病毒载体的产生，使病毒生产的要求与GALV在人类细胞中的细胞毒性作用相协调，并且在分裂和静止的肿瘤细胞上均具有高滴度。直接瘤内注射这些病毒液可根除逐渐生长的人肿瘤异种移植瘤。FMG转基因的强大旁观者效应是该方法成功的主要因素，但免疫激活也可能是一个因素。据我们所知，这是体内首次证明FMG和慢病毒载体在癌症基因治疗中的潜力，并强调了探索不同载体系统以补充治疗性转基因生物学特性的重要性。
