Kastenmuller Wolfgang, Drexler Ingo, Ludwig Holger, Erfle Volker, Peschel Christian, Bernhard Helga, Sutter Gerd
GSF-Institut für Molekulare Virologie, Klinikum rechts der Isar, Technische Universität 81675 München, Germany.
Virology. 2006 Jul 5;350(2):276-88. doi: 10.1016/j.virol.2006.02.039. Epub 2006 Apr 3.
Vector-infected dendritic cells (DC) are evaluated for antigen delivery in experimental therapy of cancer and infectious diseases. Here, we investigated infections of immature or mature, monocyte-derived human DC with recombinant vaccinia virus MVA producing human Her-2/neu, a candidate tumor-associated antigen. Assessment of the molecular virus life cycle in infected DC revealed a general arrest at the level of viral early gene expression. When monitoring the phenotype of MVA-infected DC, including expression of cell surface markers, we found immature cells readily undergoing apoptosis. Nevertheless, we detected significant populations of viable DC being characterized by high level Her-2/neu expression and unimpaired display of costimulatory molecules. While infected viable immature DC failed to undergo maturation despite cytokine treatment, both DC populations efficiently presented MVA-produced target antigen. These findings allow to better define the requirements for MVA-mediated antigen delivery to DC and help to derive optimized vectors for this advanced therapy option.
在癌症和传染病的实验性治疗中，对载体感染的树突状细胞（DC）进行抗原递送评估。在此，我们研究了重组痘苗病毒MVA对未成熟或成熟的单核细胞衍生的人DC的感染情况，该重组痘苗病毒MVA可产生人Her-2/neu，这是一种候选肿瘤相关抗原。对感染DC中分子病毒生命周期的评估显示，病毒早期基因表达水平普遍停滞。在监测MVA感染的DC的表型（包括细胞表面标志物的表达）时，我们发现未成熟细胞容易发生凋亡。然而，我们检测到大量存活的DC，其特征是高水平的Her-2/neu表达以及共刺激分子的正常展示。尽管进行了细胞因子处理，但感染的存活未成熟DC未能成熟，而这两种DC群体均能有效地呈递MVA产生的靶抗原。这些发现有助于更好地确定MVA介导的抗原递送至DC的要求，并有助于为这种先进的治疗方案开发优化的载体。
