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Blood, 5 November 2009, Vol. 114, No. 19, pp. 4142-4149. Prepublished online as a Blood First Edition Paper on September 11, 2009; DOI 10.1182/blood-2009-05-219683. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-05-219683v1 114/19/4142    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 CrossRef Google Scholar Articles by Qin, H. Articles by Kwak, L. W. PubMed PubMed Citation Articles by Qin, H. Articles by Kwak, L. W. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Vaccine site inflammation potentiates idiotype DNA vaccine-induced therapeutic T cell–, and not B cell–, dependent antilymphoma immunity Hong Qin1,2,*, Soung-chul Cha1,2,*, Sattva S. Neelapu1,2, Yanyan Lou2,3, Jinsong Wei1,2, Yong-Jun Liu2,4, and Larry W. Kwak1,2 1 Department of Lymphoma and Myeloma, 2 Center for Cancer Immunology Research, 3 Department of Melanoma, and 4 Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston Lymphoma idiotype protein vaccines have shown therapeutic potential in previous clinical studies, and results from a completed pivotal, phase 3 controlled trial are promising. However, streamlined production of these patient-specific vaccines is required for eventual clinical application. Here, we show that second-generation, chemokine-fused idiotype DNA vaccines, when combined with myotoxins that induced sterile inflammation with recruitment of antigen-presenting cells at vaccination sites, were exceptional in their ability to provoke memory antitumor immunity in mice, compared with several TLR agonists. The combined vaccination strategy elicited both antigen-specific T-cell responses and humoral immunity. Unexpectedly, vaccine-induced tumor protection was intact in B cell–deficient mice but was abrogated completely by T-cell depletion in vivo, suggesting T-cell dependence. Furthermore, the optimal effect of myotoxins was observed with fusion vaccines that specifically targeted antigen delivery to antigen-presenting cells and not with vaccines lacking a targeting moiety, suggesting that the rational vaccine design will require combination strategies with novel, proinflammatory agents and highly optimized molecular vaccine constructs. These studies also challenge the paradigm that antibody responses are the primary of idiotype-specific antitumor effects and support the optimization of idiotype vaccines designed to induce primarily T-cell immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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