title: Trial Watch: Toll-like receptor agonists in oncological indications.
abstract: Toll-like receptors (TLRs) are an evolutionarily conserved group of enzymatically inactive, single membrane-spanning proteins that recognize a wide panel of exogenous and endogenous danger signals. Besides constituting a crucial component of the innate immune response to bacterial and viral pathogens, TLRs appear to play a major role in anticancer immunosurveillance. In line with this notion, several natural and synthetic TLR ligands have been intensively investigated for their ability to boost tumor-targeting immune responses elicited by a variety of immunotherapeutic and chemotherapeutic interventions. Three of these agents are currently approved by the US Food and Drug Administration (FDA) or equivalent regulatory agencies for use in cancer patients: the so-called bacillus Calmette-Guérin, monophosphoryl lipid A, and imiquimod. However, the number of clinical trials testing the therapeutic potential of both FDA-approved and experimental TLR agonists in cancer patients is stably decreasing, suggesting that drug developers and oncologists are refocusing their interest on alternative immunostimulatory agents. Here, we summarize recent findings on the use of TLR agonists in cancer patients and discuss how the clinical evaluation of FDA-approved and experimental TLR ligands has evolved since the publication of our first Trial Watch dealing with this topic.
authors.affiliation: Gustave Roussy; Villejuif, France ; INSERM, UMRS1138; Paris, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France ; Université Paris-Sud/Paris XI; Paris, France.
authors.forename: Fernando
authors.initials: F
authors.lastname: Aranda
authors.affiliation: Gustave Roussy; Villejuif, France ; INSERM, UMRS1138; Paris, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France ; Université Paris-Sud/Paris XI; Paris, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.affiliation: Gustave Roussy; Villejuif, France ; INSERM, UMRS1138; Paris, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France ; Université Paris-Sud/Paris XI; Paris, France.
authors.forename: Florine
authors.initials: F
authors.lastname: Obrist
authors.affiliation: Gustave Roussy; Villejuif, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.affiliation: INSERM, UMRS1138; Paris, France ; Université Paris Descartes/Paris V, Sorbonne Paris Cité; Paris, France ; Laboratory of Integrative Cancer Immunology, Centre de Recherche des Cordeliers; Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Galon
authors.affiliation: INSERM, UMRS1138; Paris, France ; Université Paris Descartes/Paris V, Sorbonne Paris Cité; Paris, France ; Université Pierre et Marie Curie/Paris VI; Paris, France ; Equipe 13, Centre de Recherche des Cordeliers; Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.affiliation: INSERM, UMRS1138; Paris, France ; Université Pierre et Marie Curie/Paris VI; Paris, France ; Université Paris Descartes/Paris V, Sorbonne Paris Cité; Paris, France ; Equipe 13, Centre de Recherche des Cordeliers; Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
authors.affiliation: Immune Design; Seattle, WA USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Henrik Ter Meulen
authors.affiliation: Gustave Roussy; Villejuif, France ; INSERM, U1015; CICBT507; Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP; Villejuif, France ; Metabolomics and Cell Biology Platforms, Gustave Roussy; Villejuif, France ; INSERM, UMRS1138; Paris, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France ; Université Paris Descartes/Paris V, Sorbonne Paris Cité; Paris, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: Gustave Roussy; Villejuif, France ; Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers; Paris, France ; Université Paris Descartes/Paris V, Sorbonne Paris Cité; Paris, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
keywords: BCG; CpG-7909; Hiltonol™; damage-associated molecular patterns; polyI:C; resiquimod
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