title: BK virus-specific T cells for use in cellular therapy show specificity to multiple antigens and polyfunctional cytokine responses.
abstract: BACKGROUND
  BK virus (BKV) infection causes hemorrhagic cystitis posthemopoietic stem-cell transplant and graft loss in renal transplant recipients. Reactivation occurs in up to 60% of patients in both groups. Treatment-related cellular immunosuppression is a major contributor to the development of BKV-related disease, but the targets of the immune response are not well characterized. Immunotherapy by adoptive transfer of cellular effectors has been shown to be effective in controlling and preventing some virus-related diseases in transplant recipients, particularly Epstein-Barr virus and cytomegalovirus. Infusion of BKV-specific T cells may potentially reconstitute functional BKV immunity and reduce clinical complications of BKV infection.
  
  
  METHODS
  BKV-specific T cells for clinical use in adoptive immunotherapy were generated using monocyte-derived dendritic cells pulsed with overlapping peptide mixes spanning the five BKV proteins VP1, VP2, VP3, large T antigen, and small T antigen. Phenotypic and functional characteristics of the cells were investigated as well as their antigen specificity.
  
  
  RESULTS
  Expanded CD4(+) and CD8(+) cells responded to restimulation with BKV peptides principally from VP1, large T, or small T antigens; produced multiple cytokines; and showed cytotoxic activity against antigen-coated targets.
  
  
  CONCLUSIONS
  Possible clinical uses for BKV-specific T cells generated using this method include immune reconstitution posthemopoietic stem-cell transplantation or prophylaxis and treatment of immune deficiency in renal transplant recipients, fulfilling the need for effective therapy for BKV-related hemorrhagic cystitis and renal dysfunction.
authors: Westmead Institute of Cancer Research, Westmead Millennium Institute, University of Sydney, Westmead, Australia. emily_blyth@wmi.usyd.edu.au
authors: Emily
authors: E
authors: Blyth
authors: Leighton
authors: L
authors: Clancy
authors: Renee
authors: R
authors: Simms
authors: Shivashni
authors: S
authors: Gaundar
authors: Philip
authors: P
authors: O'Connell
authors: Kenneth
authors: K
authors: Micklethwaite
authors: David J
authors: DJ
authors: Gottlieb
mesh_terms: D000956:Antigens, Viral / Q000276:immunology*; D001739:BK Virus / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D052118:Lysosomal-Associated Membrane Protein 1 / Q000097:blood; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D016207:Cytokines; D000939:Epitopes; D052118:Lysosomal-Associated Membrane Protein 1