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Blood, 15 March 2008, Vol. 111, No. 6, pp. 3116-3125. Prepublished online as a Blood First Edition Paper on January 17, 2008; DOI 10.1182/blood-2007-09-114371. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-09-114371v1 111/6/3116    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 Ahonen, C. L. Articles by Noelle, R. J. Search for Related Content PubMed PubMed Citation Articles by Ahonen, C. L. Articles by Noelle, R. J. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared with unitary adjuvants as cancer vaccines Cory L. Ahonen1,2, Anna Wasiuk1,2, Shinichiro Fuse1, Mary Jo Turk1,2, Marc S. Ernstoff3, Arief A. Suriawinata4, James D. Gorham1,5, Ross M. Kedl6, Edward J. Usherwood1, and Randolph J. Noelle1,2 1 Department of Microbiology & Immunology, Dartmouth Medical School and the 2 Norris Cotton Cancer Center, Lebanon, NH; 3 Medical Oncology Immunotherapy Group, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 4 Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH; 5 Department of Pathology, Dartmouth Medical School, Lebanon, NH; and 6 Integrated Department of Immunology, University of Colorado Health Sciences Center, Denver Identification of Toll-like receptors (TLRs) and their ligands, and tumor necrosis factor–tumor necrosis factor receptor (TNF-TNFR) pairs have provided the first logical, hypothesis-based strategies to molecularly concoct adjuvants to elicit potent cell-mediated immunity via activation of innate and adaptive immunity. However, isolated activation of one immune pathway in the absence of others can be toxic, ineffective, and detrimental to long-term, protective immunity. Effective engineered vaccines must include agents that trigger multiple immunologic pathways. Here, we report that combinatorial use of CD40 and TLR agonists as a cancer vaccine, compared with monotherapy, elicits high frequencies of self-reactive CD8+ T cells, potent tumor-specific CD8+ memory, CD8+ T cells that efficiently infiltrate the tumor-burdened target organ; therapeutic efficacy; heightened ratios of CD8+ T cells to FoxP3+ cells at the tumor site; and reduced hepatotoxicity. These findings provide intelligent strategies for the formulation of multifactorial vaccines to achieve maximal efficacy in cancer vaccine trials in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. S. Raman, J. O'Donnell, H. R. Bailor, W. Goto, R. Lahiri, T. P. Gillis, S. G. Reed, and M. S. 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Cortesini, and N. Suciu-Foca Ig-Like Transcript 3 Regulates Expression of Proinflammatory Cytokines and Migration of Activated T Cells J. Immunol., May 1, 2009; 182(9): 5208 - 5216. [Abstract] [Full Text] [PDF] S. Fuse, C.-Y. Tsai, M. J. Molloy, S. R. Allie, W. Zhang, H. Yagita, and E. J. Usherwood Recall Responses by Helpless Memory CD8+ T Cells Are Restricted by the Up-Regulation of PD-1 J. Immunol., April 1, 2009; 182(7): 4244 - 4254. [Abstract] [Full Text] [PDF] C. Haluszczak, A. D. Akue, S. E. Hamilton, L. D.S. Johnson, L. Pujanauski, L. Teodorovic, S. C. Jameson, and R. M. Kedl The antigen-specific CD8+ T cell repertoire in unimmunized mice includes memory phenotype cells bearing markers of homeostatic expansion J. Exp. Med., February 16, 2009; 206(2): 435 - 448. [Abstract] [Full Text] [PDF] E. L. J. M. Smits, P. Ponsaerts, Z. N. Berneman, and V. F. I. 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