title: Increase of in vivo antitumoral activity by CD40L (CD154) gene transfer into pancreatic tumor cell-dendritic cell hybrids.
abstract: OBJECTIVE
  Fusion of dendritic cells (DC) with tumor cells is an approach in immunotherapy combining antigenicity and capacity of antigen presentation to activate T cells for the induction of tumor-specific cytotoxic immunity. Although there have been reports of clinical benefit, response rates have been limited and further improvements are warranted.
  
  
  METHODS
  We used murine DC and a novel protocol for an effective fusion of those cells with the murine pancreatic cell line Panc02.
  
  
  RESULTS
  We observed 2 events: only moderate in vitro and in vivo cytotoxicity of tumor cell/DC hybrids and a down-regulation of costimulatory molecules on fused cells. Therefore, we transfected tumor cell/DC hybrids with an adenovirus expressing CD154 to improve DC activation and generating antitumor immune response without the need of CD4 T cells. High CD154 expression could be obtained by transfection of DC and Panc02 cells prior fusion. Furthermore, vaccination with CD154-transfected tumor cell/DC hybrid led to a significantly increased induction of cytotoxic T cells in vitro and to an improved antitumoral effect in an orthotopic in vivo mouse model.
  
  
  CONCLUSIONS
  CD154-transfected tumor cell/DC hybrids are a promising approach to increase the efficiency of antitumoral response.
authors: Department of Internal Medicine I, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
authors: Carsten
authors: C
authors: Ziske
authors: Patricia E
authors: PE
authors: Etzrodt
authors: Alex-S
authors: AS
authors: Eliu
authors: Marcus
authors: M
authors: Gorschlüter
authors: John
authors: J
authors: Strehl
authors: Dimitri
authors: D
authors: Flieger
authors: Davorka
authors: D
authors: Messmer
authors: Volker
authors: V
authors: Schmitz
authors: Maria A
authors: MA
authors: Gonzalez-Carmona
authors: Elisabeth
authors: E
authors: Sievers
authors: Peter
authors: P
authors: Brossart
authors: Tilman
authors: T
authors: Sauerbruch
authors: Ingo G H
authors: IG
authors: Schmidt-Wolf
mesh_terms: D000818:Animals; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006822:Hybrid Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D016219:Immunotherapy, Adoptive / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014162:Transfection
chemical_list: D023201:CD40 Ligand