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Blood, 15 September 2007, Vol. 110, No. 6, pp. 1797-1805. Prepublished online as a Blood First Edition Paper on May 31, 2007; DOI 10.1182/blood-2006-06-032938. This Article Full Text Full Text (PDF) Supplemental Methods and Table All Versions of this Article: blood-2006-06-032938v1 110/6/1797    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fredriksen, A. B. Articles by Bogen, B. Search for Related Content PubMed PubMed Citation Articles by Fredriksen, A. B. Articles by Bogen, B. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Chemokine-idiotype fusion DNA vaccines are potentiated by bivalency and xenogeneic sequences Agnete Brunsvik Fredriksen1,2, and Bjarne Bogen1,2 1 Institute of Immunology, University of Oslo; 2 Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway V regions of monoclonal Ig express an exquisite B-cell tumor–specific antigen called idiotype (Id). Id is a weak antigen and it is important to improve immunogenicity of Id vaccines. Chemokine receptors are expressed on antigen-presenting cells (APCs) and are promising targets for Id vaccines. Here we compare monomeric and dimeric forms of MIP-1 and RANTES that target Id to APCs in a mouse B lymphoma (A20) and a multiple myeloma model (MOPC315). MIP-1 was more potent than RANTES. The dimeric proteins were more potent than monomeric equivalents in short-term assays. When delivered in vivo by intramuscular injection of plasmids followed by electroporation, dimeric proteins efficiently primed APCs in draining lymph nodes for activation and proliferation of Id-specific CD4+ T cells. Good anti-Id antibody responses were obtained, and mice immunized only once were 60% to 80% protected in both tumor models. CD8+ T cells contributed to the protection. Antibody responses and tumor protection were reduced when the human Ig hinge = CH3 dimerization motif was replaced with syngeneic mouse counterparts, indicating that tumor-protective responses were dependent on xenogeneic sequences. The results suggest that bivalency and foreign sequences combine to increase the efficiency of chemokine-Id DNA vaccines. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Tunheim, K. W. Schjetne, I. B. Rasmussen, L. M. Sollid, I. Sandlie, and B. Bogen Recombinant antibodies for delivery of antigen: a single loop between {beta}-strands in the constant region can accommodate long, complex and tandem T cell epitopes Int. Immunol., March 1, 2008; 20(3): 295 - 306. [Abstract] [Full Text] [PDF]

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