title: Inhibition of human diffuse large B-cell lymphoma growth by JC polyomavirus-like particles delivering a suicide gene.
abstract: BACKGROUND
  Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of aggressive B-cell non-Hodgkin lymphoma. About one-third of patients are either refractory to the treatment or experience relapse afterwards, pointing to the necessity of developing other effective therapies for DLBCL. Human B-lymphocytes are susceptible to JC polyomavirus (JCPyV) infection, and JCPyV virus-like particles (VLPs) can effectively deliver exogenous genes to susceptible cells for expression, suggesting the feasibility of using JCPyV VLPs as gene therapy vectors for DLBCL.
  
  
  METHODS
  The JCPyV VLPs packaged with a GFP reporter gene were used to infect human DLBCL cells for gene delivery assay. Furthermore, we packaged JCPyV VLPs with a suicide gene encoding thymidine kinase (TK) to inhibit the growth of DLBCL in vitro and in vivo.
  
  
  RESULTS
  Here, we show that JCPyV VLPs effectively entered human germinal center B-cell-like (GCB-like) DLBCL and activated B-cell-like (ABC-like) DLBCL and expressed the packaged reporter gene in vitro. As measured by the MTT assay, treatment with tk-VLPs in combination with gancyclovir (GCV) reduced the viability of DLBCL cells by 60%. In the xenograft mouse model, injection of tk-VLPs through the tail vein in combination with GCV administration resulted in a potent 80% inhibition of DLBCL tumor nodule growth.
  
  
  CONCLUSIONS
  Our results demonstrate the effectiveness of JCPyV VLPs as gene therapy vectors for human DLBCL and provide a potential new strategy for the treatment of DLBCL.
authors.affiliation: Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan. 04105@cych.org.tw.|Department of Pediatrics, Chiayi Christian Hospital, Chiayi, Taiwan. 04105@cych.org.tw.
authors.forename: Chun-Nun
authors.initials: CN
authors.lastname: Chao
authors.affiliation: Department of Medical Research, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan. huangyl@tzuchi.com.tw.
authors.forename: Yih-Leh
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan. k920492@gmail.com.|Department of Urology, Chiayi Christian Hospital, Chiayi, Taiwan. k920492@gmail.com.
authors.forename: Mien-Chun
authors.initials: MC
authors.lastname: Lin
authors.affiliation: Department of Medical Research, Chiayi Christian Hospital, Chiayi, Taiwan. fcyo@ms72.hinet.net.
authors.forename: Chiung-Yao
authors.initials: CY
authors.lastname: Fang
authors.affiliation: Department of Urology, Chiayi Christian Hospital, Chiayi, Taiwan. 01712@cych.org.tw.
authors.forename: Cheng-Huang
authors.initials: CH
authors.lastname: Shen
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan. plchen@ctust.edu.tw.
authors.forename: Pei-Lain
authors.initials: PL
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan. wml@csmu.edu.tw.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Molecular Biology, National Chung Cheng University, Chiayi, Taiwan. biodcc@ccu.edu.tw.
authors.forename: Deching
authors.initials: D
authors.lastname: Chang
authors.affiliation: Department of Anatomic Pathology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan. P121521@tzuchi.com.tw.|School of Medicine, Tzu Chi University, Hualien, Taiwan. P121521@tzuchi.com.tw.
authors.forename: Chih-En
authors.initials: CE
authors.lastname: Tseng
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007577:JC Virus / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D012008:Recurrence
chemical_list: D049452:Green Fluorescent Proteins