title: Enhancing the immunogenicity of tumour lysate-loaded dendritic cell vaccines by conjugation to virus-like particles.
abstract: BACKGROUND
  Tumour cell lysates are an excellent source of many defined and undefined tumour antigens and have been used clinically in immunotherapeutic regimes but with limited success.
  
  
  METHODS
  We conjugated Mel888 melanoma lysates to rabbit haemorrhagic disease virus virus-like particles (VLP), which can act as vehicles to deliver multiple tumour epitopes to dendritic cells (DC) to effectively activate antitumour responses.
  
  
  RESULTS
  Virus-like particles did not stimulate the phenotypic maturation of DC although, the conjugation of lysates to VLP (VLP-lysate) did overcome lysate-induced suppression of DC activation. Lysate-conjugated VLP enhanced delivery of antigenic proteins to DC, while the co-delivery of VLP-lysates with OK432 resulted in cross-priming of naïve T cells, with expansion of a MART1(+) population of CD8(+) T cells and generation of a specific cytotoxic response against Mel888 tumour cell targets. The responses generated with VLP-lysate and OK432 were superior to those stimulated by unconjugated lysate with OK432.
  
  
  CONCLUSIONS
  Collectively, these results show that the combination of VLP-lysate with OK432 delivered to DC overcomes the suppressive effects of lysates, and enables priming of naïve T cells with superior ability to specifically kill their target tumour cells.
authors: Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors: S J
authors: SJ
authors: Win
authors: D G G
authors: DG
authors: McMillan
authors: F
authors: F
authors: Errington-Mais
authors: V K
authors: VK
authors: Ward
authors: S L
authors: SL
authors: Young
authors: M A
authors: MA
authors: Baird
authors: A A
authors: AA
authors: Melcher
mesh_terms: D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D013347:Subcellular Fractions; D014771:Virion / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines