期刊
GENE THERAPY
卷 17, 期 6, 页码 745-751出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2010.33
关键词
cell-based gene therapy; human endothelial cells; human mesenchimal stem cells; lentivirally transduced ECs; blood vessels; cancer
类别
资金
- Ministerio de Ciencia e Innovacion [BIO2008-03233]
- Comunidad Autonoma de Madrid [S-BIO-0236-2006]
- European Union
- Fondo de Investigacion Sanitaria [PI061621]
- Instituto de Salud Carlos III [CM06/00055]
- Comunidad Autonoma de Madrid/European Social Fund [FPI-000531]
- European Social Fund
- Gobierno Vasco [BFI07.132]
Several works have shown the feasibility of engineering functional blood vessels in vivo using human endothelial cells (ECs). Going further, we explored the therapeutic potential of neovessels after gene-modifying the ECs for the secretion of a therapeutic protein. Given that these vessels are connected with the host vascular bed, we hypothesized that systemic release of the expressed protein is immediate. As a proof of principle, we used primary human ECs transduced with a lentiviral vector for the expression of a recombinant bispecific alpha CEA/alpha CD3 antibody. These ECs, along with mesenchymal stem cells as a source of mural cells, were embedded in Matrigel and subcutaneously implanted in nude mice. High antibody levels were detected in plasma for 1 month. Furthermore, the antibody exerted a therapeutic effect in mice bearing distant carcinoembryonic-antigen (CEA)-positive tumors after inoculation of human T cells. In summary, we show for the first time the therapeutic effect of a protein locally secreted by engineered human neovessels. Gene Therapy (2010) 17, 745-751; doi: 10.1038/gt.2010.33; published online 25 March 2010
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据