The pharmacokinetics of Toll-like receptor agonists and the impact on the immune system

Expert Rev Clin Pharmacol. 2011 Mar;4(2):275-89. doi: 10.1586/ecp.11.5.


Toll-like receptor (TLR) ligation activates both the innate and adaptive immune systems, and plays an important role in antiviral and anti-tumor immunity. Therefore, a significant amount of effort has been devoted to exploit the therapeutic potential of TLR agonists. Depending on the therapeutic purpose, either as adjuvants to vaccine, chemotherapy or standalone therapy, TLR agonists have been administered via different routes. Both preclinical and clinical studies have suggested that the route of administration has significant effects on pharmacokinetics, and that understanding these effects is critical to the success of TLR agonist drug development. This article will summarize the pharmacokinetics of TLR agonists with different administration routes, with an emphasis on clinical studies of TLR ligands in oncologic applications.

Keywords: CpG; TLR agonist; Toll-like receptor; imiquimod; immune response; immunotherapy; pharmacokinetics; poly I:C; resiquimod.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / pharmacokinetics*
  • Animals
  • Clinical Trials as Topic / methods
  • Drug Delivery Systems / methods
  • Humans
  • Immune System / drug effects*
  • Immune System / immunology
  • Immune System / metabolism
  • Ligands
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Toll-Like Receptors / agonists*
  • Toll-Like Receptors / metabolism


  • Adjuvants, Immunologic
  • Ligands
  • Toll-Like Receptors