title: Targeted DNA vaccines eliciting crossreactive anti-idiotypic antibody responses against human B cell malignancies in mice.
abstract: BACKGROUND
  Therapeutic idiotypic (Id) vaccination is an experimental treatment for selected B cell malignancies. A broader use of Id-based vaccination, however, is hampered by the complexity and costs due to the individualized production of protein vaccines. These limitations may be overcome by targeted DNA vaccines encoding stereotyped immunoglobulin V regions of B cell malignancies. We have here investigated whether such vaccines might elicit cross-reactive immune responses thus offering the possibility to immunize subsets of patients with the same vaccine.
  
  
  METHODS
  Fusion vaccines targeting patient Id to mouse Major Histocompatibility Complex (MHC) class II molecules (chimeric mouse/human) or chemokine receptors (fully human) on antigen-presenting cells (APC) were genetically constructed for two Chronic Lymphocytic Leukemia (CLL) patients and one prototypic stereotyped B-cell receptor (BCR) commonly expressed by Hepatitis C Virus (HCV)-associated Non Hodgkin Lymphoma (NHL). The A20 murine B lymphoma cells were engineered to express prototypic HCV-associated B cell lymphoma BCR. Anti-Id antibody responses were studied against stereotyped and non-stereotyped BCRs on CLL patients' cells as well as transfected A20 cells.
  
  
  RESULTS
  DNA vaccination of mice with Id vaccines that target APC elicited increased amounts of antibodies specific for the patient's Id as compared with non targeted control vaccines. Anti-Id antibodies cross-reacted between CLL cells with closely related BCR. A20 cells engineered to express patients' V regions were not tumorigenic in mice, preventing tumor challenge experiments.
  
  
  CONCLUSIONS
  These findings provide experimental support for use of APC-targeted fusion Id DNA vaccines for the treatment of B cell lymphoma and CLL that express stereotyped BCRs.
authors: Department of Immunology, Centre for Immune Regulation, University of Oslo, Oslo University Hospital, Rikshospitalet, NO-0424 Oslo, Norway. pieradelchi.ruffini@virgilio.it.
authors: Pier Adelchi
authors: PA
authors: Ruffini
authors: Audun
authors: A
authors: Os
authors: Riccardo
authors: R
authors: Dolcetti
authors: Geir E
authors: GE
authors: Tjønnfjord
authors: Ludvig A
authors: LA
authors: Munthe
authors: Bjarne
authors: B
authors: Bogen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003429:Cross Reactions / Q000276:immunology*; D004195:Disease Models, Animal; D016174:Hepacivirus / Q000276:immunology; D006801:Humans; D007114:Immunization; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D019496:Cancer Vaccines; D011947:Receptors, Antigen, B-Cell; D019707:Receptors, Chemokine; D019444:Vaccines, DNA