Strobel I, Krumbholz M, Menke A, Hoffmann E, Dunbar P R, Bender A, Hobom G, Steinkasserer A, Schuler G, Grassmann R
Department of Dermatology, University of Erlangen-Nürnberg, D-91052 Erlangen, Germany.
Hum Gene Ther. 2000 Nov 1;11(16):2207-18. doi: 10.1089/104303400750035735.
Dendritic cells (DCs) are the most potent inducers of immune reactions. Genetically modified DCs, which express tumor-associated antigens (TAA), can efficiently induce antitumor immunity and thus have a high potential as tools in cancer therapy. The gene delivery is most efficiently achieved by viral vectors. Here, we explored the capacity of influenza virus vectors to transduce TAA genes. These viruses abortively infect DCs without interfering with their antigen-presenting capacity. In contrast to other viruses used for DC transduction, influenza viruses can be efficiently controlled by antiviral pharmaceuticals, lack the ability to integrate into host chromosomes, and fail to establish persistent infections. Genes encoding a melanoma-derived TAA (MAGE-3), or the green fluorescence protein (GFP), were introduced into a high-expression avian influenza virus vector. Monocyte-derived mature DCs infected by these recombinants efficiently produced GFP or MAGE-3. More than 90% of the infected DCs can express a transduced gene. Importantly, these transduced DCs retained their characteristic phenotype and their potent allogeneic T cell stimulatory capacity, and were able to stimulate MAGE-3-specific CD8(+) cytotoxic T cells. Thus influenza virus vectors provide a highly efficient gene delivery system in order to transduce human DCs with TAA, which consequently stimulate TAA-specific T cells.
树突状细胞（DCs）是免疫反应最有效的诱导剂。表达肿瘤相关抗原（TAA）的基因修饰DCs能够有效诱导抗肿瘤免疫，因此作为癌症治疗工具具有很大潜力。基因传递通过病毒载体能最有效地实现。在此，我们探究了流感病毒载体转导TAA基因的能力。这些病毒能使DCs流产感染而不干扰其抗原呈递能力。与用于DC转导的其他病毒不同，流感病毒能被抗病毒药物有效控制，缺乏整合到宿主染色体的能力，且无法建立持续性感染。将编码黑色素瘤来源的TAA（MAGE - 3）或绿色荧光蛋白（GFP）的基因导入高表达禽流感病毒载体。被这些重组体感染的单核细胞衍生的成熟DCs能高效产生GFP或MAGE - 3。超过90%的感染DCs能表达转导基因。重要的是，这些转导的DCs保留了其特征性表型及其强大的同种异体T细胞刺激能力，并能够刺激MAGE - 3特异性CD8(+)细胞毒性T细胞。因此，流感病毒载体提供了一种高效的基因传递系统，以便用TAA转导人DCs，从而刺激TAA特异性T细胞。
