targeted dna vaccines for enhanced induction of idiotype (id)-specific b and t cells

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2012
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Abstract
Background: Idiotopes (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-MHCII, 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 4 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.
Reference Key
fredriksen2012frontierstargeted Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Agnete Brunsvik Fredriksen;Inger eSandlie;Bjarne eBogen
Journal international journal of heat and technology
Year 2012
DOI
10.3389/fonc.2012.00154
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