Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 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
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Figures
Right arrow All Versions of this Article:
blood-2007-09-114371v1
111/6/3116    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ahonen, C. L.
Right arrow Articles by Noelle, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ahonen, C. L.
Right arrow Articles by Noelle, R. J.
Related Collections
Right arrow Immunobiology
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020