Pfirschke Christina, Schirrmacher Volker
Division of Cellular Immunology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Int J Oncol. 2009 Apr;34(4):951-62. doi: 10.3892/ijo_00000221.
Oncolytic virotherapy, a new type of cancer therapy involving viruses with oncolytic and immunostimulatory potential, is based on tumor selective viral replication, resulting in a specific lysis of tumor cells. Effective tumor targeting of oncolytic viruses remains a major problem because only a fraction of systemically applied viruses can reach the tumor tissue. We describe for the first time in an in vitro co-culture system that T lymphocytes can be loaded with Newcastle disease virus (NDV) in such a way that the virus load will be transferred to the tumor target cells upon contact of the T cells with tumor cells. The effectiveness of this NDV 'hitchhiking' on T cells can be influenced by the amount of virus, the ratio of T cells to tumor cells, the activation status of the T cells and by the virulence of the virus as shown by flow cytometry, quantitative real-time PCR and fluorescence microscopy. In a tumor neutralization assay in vitro, monolayers of human tumor cells could be completely and effectively destroyed by the addition of polyclonally activated human T cells loaded with oncolytic NDV. This process involves the formation of large T cell clusters as revealed by phase-contrast microscopy. Loading of oncolytic NDV onto activated T cells and adoptive transfer into a tumor-bearing host might enhance the efficacy of adoptive T cell therapy of tumors as well as tumor targeting of oncolytic viruses.
溶瘤病毒疗法是一种新型癌症治疗方法，涉及具有溶瘤和免疫刺激潜力的病毒，其基于肿瘤选择性病毒复制，导致肿瘤细胞的特异性裂解。溶瘤病毒有效靶向肿瘤仍然是一个主要问题，因为全身应用的病毒只有一小部分能够到达肿瘤组织。我们首次在体外共培养系统中描述，T淋巴细胞可以以这样一种方式装载新城疫病毒（NDV），即当T细胞与肿瘤细胞接触时，病毒载体会转移到肿瘤靶细胞上。通过流式细胞术、定量实时PCR和荧光显微镜观察发现，这种NDV“搭便车”在T细胞上的有效性会受到病毒量、T细胞与肿瘤细胞的比例、T细胞的激活状态以及病毒毒力的影响。在体外肿瘤中和试验中，添加装载有溶瘤性NDV的多克隆激活的人T细胞可以完全有效地破坏人肿瘤细胞单层。相差显微镜显示，这个过程涉及大T细胞簇的形成。将溶瘤性NDV装载到活化的T细胞上并过继转移到荷瘤宿主中，可能会提高肿瘤过继性T细胞疗法的疗效以及溶瘤病毒对肿瘤的靶向性。
