Cross-infection of tumor cells by contact with T lymphocytes loaded with Newcastle disease virus.
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.
Pfirschke
Christina
C
Division of Cellular Immunology, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
Schirrmacher
Volker
V
D000818:Animals; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008856:Microscopy, Fluorescence / Q000379:methods; D008858:Microscopy, Phase-Contrast / Q000379:methods; D008954:Models, Biological; D009522:Newcastle disease virus / Q000378:metabolism*; D050130:Oncolytic Virotherapy / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology*