title: Targeted idiotype-fusion DNA vaccines for human multiple myeloma: preclinical testing.
abstract: OBJECTIVE
  A homodimeric fusion DNA vaccine targeting idiotype (Id) to antigen-presenting cells (APC) induced robust tumor protection in a mouse model of multiple myeloma (MM). Similar Id vaccine molecules were generated for four patients with MM with three main objectives: (i) do the vaccine molecules induce bona fide anti-Id immune responses in mice? (ii) does targeting of the vaccine molecules to APC enhance immune responses? (iii) can anti-Id antibodies, generated as by-product in vaccinated mice, be used to establish sensitive assays for complete remission (CR) prior to patient vaccination?
  
  
  METHODS
  Chimeric vaccine molecules targeting patient Id to mouse major histocompatibility complex (MHC) class II molecules were genetically constructed for four patients with MM.
  
  
  RESULTS
  DNA vaccination of mice with chimeric vaccines targeting patient Id to mouse MHC class II molecules elicited antibodies specific for the patient's myeloma protein. Targeting MHC class II greatly enhanced anti-Id responses. Mouse anti-Id antibodies were used to establish myeloma protein-specific enzyme-linked immunosorbent assays (ELISAs) that were between 75 and 1500 times more sensitive than conventional serum protein electrophoresis and immunofixation.
  
  
  CONCLUSIONS
  These results pave the way for testing targeted DNA Id vaccines in patients in CR. Id- and patient-specific ELISA could be established affording evaluation of CR depth beyond current serological methods.
authors.affiliation: Centre for Immune Regulation, Institute of Immunology, University of Oslo and Rikshospitalet Oslo University Hospital Section of Hematology, Medical Department, Rikshospitalet Oslo University Hospital, Oslo, Norway.
authors.forename: Marianne
authors.initials: M
authors.lastname: Frøyland
authors.forename: Pier Adelchi
authors.initials: PA
authors.lastname: Ruffini
authors.forename: Keith Michael
authors.initials: KM
authors.lastname: Thompson
authors.forename: Tobias
authors.initials: T
authors.lastname: Gedde-Dahl
authors.forename: Agnete Brunsvik
authors.initials: AB
authors.lastname: Fredriksen
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D000918:Antibody Specificity; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D009194:Myeloma Proteins / Q000032:analysis / Q000276:immunology; D010954:Plasmacytoma / Q000235:genetics / Q000276:immunology / Q000628:therapy; D012074:Remission Induction; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D000949:Histocompatibility Antigens Class II; D009194:Myeloma Proteins; D019444:Vaccines, DNA