Clinical investigations of Toll-like receptor agonists

Thomas Meyer, Eggert Stockfleth
Expert Opinion on Investigational Drugs 2008, 17 (7): 1051-65

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.

RESULTS/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.

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