title: Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells.
abstract: BACKGROUND
  Idiotypes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id(+) tumors. However, vaccine strategies that enhance Id-specific responses are needed.
  
  
  METHODS
  Id(+) single-chain fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen-presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHC II, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation.
  
  
  RESULTS
  (i) Transfected cells secreted plasmid-encoded Id(+) fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id(+) tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id(+) scFv from four multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro. (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented.
  
  
  CONCLUSIONS
  Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.
authors.affiliation: Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital Oslo, Norway.
authors.forename: Agnete B
authors.initials: AB
authors.lastname: Fredriksen
authors.forename: Inger
authors.initials: I
authors.lastname: Sandlie
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
keywords: antigen-presenting cells; idiotype; lymphoma; multiple myeloma; vaccine