SEARCH:   Advanced

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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 24, 2007 Accepted January 7, 2008 Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared to unitary adjuvants as cancer vaccines Cory L Ahonen, Anna Wasiuk, Shinichiro Fuse, Mary Jo Turk, Marc S Ernstoff, Arief A Suriawinata, James D Gorham, Ross M Kedl, Edward J Usherwood, and Randolph J. Noelle* Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH, United States Norris Cotton Cancer Center, Lebanon, NH, United States Medical Oncology Immunotherapy Group, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States Department of Pathology, Dartmouth Medical School, Lebanon, NH, United States Integrated Department of Immunology, University of Colorado Health Sciences Center, Denver, CO, United States * Corresponding author; email: rjn{at}dartmouth.edu. Identification of Toll-like Receptors (TLR) and their ligands, and 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, as compared to 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. Duthie Vaccination with the ML0276 Antigen Reduces Local Inflammation but Not Bacterial Burden during Experimental Mycobacterium leprae Infection Infect. Immun., December 1, 2009; 77(12): 5623 - 5630. [Abstract] [Full Text] [PDF] M. Gil, M. Bieniasz, A. Wierzbicki, B. J. Bambach, H. Rokita, and D. Kozbor Targeting a Mimotope Vaccine to Activating Fc{gamma} Receptors Empowers Dendritic Cells to Prime Specific CD8+ T Cell Responses in Tumor-Bearing Mice J. Immunol., November 15, 2009; 183(10): 6808 - 6818. [Abstract] [Full Text] [PDF] U. K. Scarlett, J. R. Cubillos-Ruiz, Y. C. Nesbeth, D. G. Martinez, X. Engle, A. T. Gewirtz, C. L. Ahonen, and J. R. Conejo-Garcia In situ Stimulation of CD40 and Toll-like Receptor 3 Transforms Ovarian Cancer-Infiltrating Dendritic Cells from Immunosuppressive to Immunostimulatory Cells Cancer Res., September 15, 2009; 69(18): 7329 - 7337. [Abstract] [Full Text] [PDF] C.-C. Chang, Z. Liu, G. Vlad, H. Qin, X. Qiao, D. M. Mancini, C. C. Marboe, R. 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. Van Tendeloo The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy Oncologist, August 1, 2008; 13(8): 859 - 875. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020