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PMID: 22934262 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Trial Watch: Experimental Toll-like receptor agonists for cancer therapy.

Oncoimmunology ·Vol. 1 ·No. 5 ·2012-08-01 ·Pages 699-716

Galluzzi L, Vacchelli E, Eggermont A, Fridman WH, Galon J, Sautès-Fridman C, Tartour E, Zitvogel L, Kroemer G

Abstract

Toll-like receptors (TLRs) are prototypic pattern recognition receptors (PRRs) best known for their ability to activate the innate immune system in response to conserved microbial components such as lipopolysaccharide and double-stranded RNA. Accumulating evidence indicates that the function of TLRs is not restricted to the elicitation of innate immune responses against invading pathogens. TLRs have indeed been shown to participate in tissue repair and injury-induced regeneration as well as in adaptive immune responses against cancer. In particular, TLR4 signaling appears to be required for the efficient processing and cross-presentation of cell-associated tumor antigens by dendritic cells, which de facto underlie optimal therapeutic responses to some anticancer drugs. Thus, TLRs constitute prominent therapeutic targets for the activation/intensification of anticancer immune responses. In line with this notion, long-used preparations such as the Coley toxin (a mixture of killed Streptococcus pyogenes and Serratia marcescens bacteria) and the bacillus Calmette-Guérin (BCG, an attenuated strain of Mycobacterium bovis originally developed as a vaccine against tuberculosis), both of which have been associated with consistent anticancer responses, potently activate TLR2 and TLR4 signaling. Today, besides BCG, only one TLR agonist is FDA-approved for therapeutic use in cancer patients: imiquimod. In this Trial Watch, we will briefly present the role of TLRs in innate and cognate immunity and discuss the progress of clinical studies evaluating the safety and efficacy of experimental TLR agonists as immunostimulatory agents for oncological indications.

Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Galluzzi Lorenzo
Université Paris Descartes/Paris V; Sorbonne Paris Cité; Paris, France ; Institut Gustave Roussy; Villejuif, France.
Vacchelli Erika
Eggermont Alexander
Fridman Wolf Hervé
Galon Jerome
Sautès-Fridman Catherine
Tartour Eric
Zitvogel Laurence
Kroemer Guido
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Article Info
Journal
Oncoimmunology
Abbr.
Oncoimmunology
ISSN
2162-4011
DOI
10.4161/onci.20696
Published
2012-08-01
Pages
699-716
Language
English
Region
United States
NLM ID
101570526
PMCID
PMC3429574
External Links
PubMed source DOI: 10.4161/onci.20696 PMC Full Text
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