Clinical investigations of Toll-like receptor agonists.
BACKGROUND
Toll-like receptors (TLR) represent a family of surface molecules that function as primary sensors of the innate immune system to recognize microbial pathogens. Ligand binding to TLR results in activation of cellular signaling pathways that regulate expression of genes involved in inflammation and immunity.


OBJECTIVE
Use of synthetic TLR ligands (agonists) for treatment and prevention of infectious and neoplastic diseases.


METHODS
Review of literature about clinical investigations of agonists of TLR 4, 7, 8, and 9.


CONCLUSIONS
Imiquimod was the first TLR agonist approved for treatment of anogenital warts, actinic keratosis and superficial basal cell carcinoma in humans. Several other agonists of TLRs 4, 7, 8 and 9 were also shown to be effective for treatment of infections and cancers and, furthermore, were used as adjuvants for vaccination. Based on safety and efficacy of the TLR agonists used to date, applications are likely to increase in the future.
University of Hamburg, University Hospital Hamburg-Eppendorf, Institute of Medical Microbiology, Virology and Hygiene, Martinistrasse 52, 20246 Hamburg, Germany. th.meyer@uke.de
Thomas
T
Meyer
Eggert
E
Stockfleth
D000276:Adjuvants, Immunologic; D000818:Animals; D006801:Humans; D007239:Infections / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D051193:Toll-Like Receptors / Q000819:agonists* / Q000378:metabolism; D014611:Vaccination
D000276:Adjuvants, Immunologic; D051193:Toll-Like Receptors