Trial Watch: Toll-like receptor agonists in oncological indications

Fernando Aranda, Erika Vacchelli, Florine Obrist, Alexander Eggermont, Jérôme Galon, Catherine Sautès-Fridman, Isabelle Cremer, Jan Henrik ter Meulen, Laurence Zitvogel, Guido Kroemer, Lorenzo Galluzzi

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Toll-like receptors (TLRs) are an evolutionarily conserved group of enzymatically inactive, single membranespanning 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.

Original languageEnglish
Article numbere29179
JournalOncoimmunology
Volume3
Issue number7
StatePublished - 2014
Externally publishedYes

Keywords

  • BCG
  • CpG-7909
  • Damage-associated molecular patterns
  • Hiltonol™
  • Polyi:C
  • Resiquimod

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