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Trial Watch: Toll-like receptor agonists in cancer immunotherapy

Author(s): Melody Smith ¹ , Elena García-Martínez ² , Michael R. Pitter ¹ , Jitka Fucikova ³ ^, ⁴ , Radek Spisek ³ ^, ⁴ , Laurence Zitvogel ⁵ ^, ⁶ ^, ⁷ ^, ⁸ , Guido Kroemer ⁹ ^, ¹⁰ ^, ¹¹ ^, ¹² ^, ¹³ , Lorenzo Galluzzi ⁹ ^, ¹⁴ ^, ¹⁵

Publication date Created: September 07 2018

Publication date (Electronic): October 11 2018

Journal: OncoImmunology

Publisher: Informa UK Limited

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Abstract

<p id="d941572e442">Toll-like receptor (TLR) agonists demonstrate therapeutic promise as immunological adjuvants for anticancer immunotherapy. To date, three TLR agonists have been approved by US regulatory agencies for use in cancer patients. Additionally, the potential of hitherto experimental TLR ligands to mediate clinically useful immunostimulatory effects has been extensively investigated over the past few years. Here, we summarize recent preclinical and clinical advances in the development of TLR agonists for cancer therapy. </p>

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Most cited references 176

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Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.

Sandra S. Diebold, Tsuneyasu Kaisho, Hiroaki Hemmi … (2004)

Interferons (IFNs) are critical for protection from viral infection, but the pathways linking virus recognition to IFN induction remain poorly understood. Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.

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The danger model: a renewed sense of self.

Polly Matzinger (2002)

For over 50 years immunologists have based their thoughts, experiments, and clinical treatments on the idea that the immune system functions by making a distinction between self and nonself. Although this paradigm has often served us well, years of detailed examination have revealed a number of inherent problems. This Viewpoint outlines a model of immunity based on the idea that the immune system is more concerned with entities that do damage than with those that are foreign.

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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

J Paavonen, P Naud, J. Salmerón … (2009)

The Lancet, 374(9686), 301-314

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Author and article information

Journal

Title: OncoImmunology

Abbreviated Title: OncoImmunology

Publisher: Informa UK Limited

ISSN (Electronic): 2162-402X

Publication date Created: September 07 2018

Publication date Created: December 02 2018

Publication date (Electronic): October 11 2018

Publication date (Print): December 02 2018

Volume: 7

Issue: 12

Page: e1526250

Affiliations

[1 ]Department of Medicine and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

[2 ]Hematology and Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain

[3 ]Sotio a.c., Prague, Czech Republic

[4 ]Department of Immunology, 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic

[5 ]INSERM, U1015, Villejuif, France

[6 ]Gustave Roussy Comprehensive Cancer Institute, Villejuif, France

[7 ]Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France

[8 ]Université Paris Sud/Paris XI, Le Kremlin-Bicêtre, France

[9 ]Université Paris Descartes/ Paris V, Paris, France

[10 ]Université Pierre et Marie Curie/Paris VI, Paris, France

[11 ]INSERM, U1138, Paris, France

[12 ]Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France

[13 ]Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France

[14 ]Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA

[15 ]Sandra and Edward Meyer Cancer Center, New York, NY, USA

Article

DOI: 10.1080/2162402X.2018.1526250

PMC ID: 6279325

PubMed ID: 30524908

SO-VID: 79b65ca5-6eac-4c2c-be3a-a7b07b692ee7

Copyright © © 2018

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