Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells
Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells
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DOI：
10.1038/nm1297
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发表时间：
2005-10-01
期刊：
影响因子：
82.9
通讯作者：
Vile, RG
中科院分区：
文献类型：
--
作者：
Cole, C;Qiao, J;Vile, RG
抗原特异性T细胞自由循环，并在抗原表达部位特异性积聚。为了增强系统递送的病毒载体的存活和靶向，我们利用了逆转录病毒颗粒非特异性地粘附或“搭便车”到T细胞表面的观察结果。抗原特异性T细胞的连续转移，加载编码白细胞介素（IL）-12或单纯疱疹病毒胸苷激酶（HSVtk）的病毒，治愈了已建立的转移性疾病，其中过继性T细胞转移单独无效。生产性移交与来自恶性肿瘤细胞和/或作为抗原激活的T细胞的结果的局部乙酰肝素酶表达相关，为体内转移性肿瘤的病毒转移提供高水平的选择性。通过吸附到细胞载体上来保护、浓缩和靶向病毒代表了用于在完全免疫活性宿主中全身递送载体的新技术，用于其中递送基因可能在治疗上有益的多种疾病。
Antigen-specific T cells circulate freely and accumulate specifically at sites of antigen expression. To enhance the survival and targeting of systemically delivered viral vectors, we exploited the observation that retroviral particles adhere nonspecifically, or 'hitchhike,' to the surface of T cells. Adoptive transfer of antigen-specific T cells, loaded with viruses encoding interleukin (IL)-12 or Herpes Simplex Virus thymidine kinase (HSVtk), cured established metastatic disease where adoptive T-cell transfer alone was not effective. Productive hand off correlated with local heparanase expression either from malignant tumor cells and/or as a result of T-cell activation by antigen, providing high levels of selectivity for viral transfer to metastatic tumors in vivo. Protection, concentration and targeting of viruses by adsorption to cell carriers represent a new technique for systemic delivery of vectors, in fully immunocompetent hosts, for a variety of diseases in which delivery of genes may be therapeutically beneficial.