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      Vaccine adjuvants as potential cancer immunotherapeutics

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          Abstract

          New adjuvants for cancer immunotherapy

          Abstract

          Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund’s adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy.

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          Most cited references79

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          STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors.

          Spontaneous T cell responses against tumors occur frequently and have prognostic value in patients. The mechanism of innate immune sensing of immunogenic tumors leading to adaptive T cell responses remains undefined, although type I interferons (IFNs) are implicated in this process. We found that spontaneous CD8(+) T cell priming against tumors was defective in mice lacking stimulator of interferon genes complex (STING), but not other innate signaling pathways, suggesting involvement of a cytosolic DNA sensing pathway. In vitro, IFN-? production and dendritic cell activation were triggered by tumor-cell-derived DNA, via cyclic-GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3). In the tumor microenvironment in vivo, tumor cell DNA was detected within host antigen-presenting cells, which correlated with STING pathway activation and IFN-? production. Our results demonstrate that a major mechanism for innate immune sensing of cancer occurs via the host STING pathway, with major implications for cancer immunotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.
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            Cancer immunotherapy: moving beyond current vaccines.

            Great progress has been made in the field of tumor immunology in the past decade, but optimism about the clinical application of currently available cancer vaccine approaches is based more on surrogate endpoints than on clinical tumor regression. In our cancer vaccine trials of 440 patients, the objective response rate was low (2.6%), and comparable to the results obtained by others. We consider here results in cancer vaccine trials and highlight alternate strategies that mediate cancer regression in preclinical and clinical models.
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              Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women

              The Lancet, 374(9686), 301-314
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                Author and article information

                Journal
                Int Immunol
                Int. Immunol
                intimm
                intimm
                International Immunology
                Oxford University Press (UK )
                0953-8178
                1460-2377
                July 2016
                22 March 2016
                22 March 2016
                : 28
                : 7 , Special Issue: Cancer Immunology—Immunotherapy
                : 329-338
                Affiliations
                1Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (iFReC), Osaka University , 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
                2Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN) , 7-6-8 Asagi, Saito, Ibaraki-City, Osaka 567-0085, Japan
                Author notes
                Correspondence to: K. J. Ishii; E-mail: kenishii@ 123456biken.osaka-u.ac.jp
                Article
                10.1093/intimm/dxw015
                4922024
                27006304
                0f5a63cb-ebd9-4dc7-b7a8-27dc9ae2313c
                © The Author 2016. Published by Oxford University Press on behalf of The Japanese Society for Immunology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 18 February 2016
                : 14 March 2016
                Page count
                Pages: 10
                Categories
                Invited Review

                Immunology
                β-glucan,combination,cpg odn,sting,tlr
                Immunology
                β-glucan, combination, cpg odn, sting, tlr

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