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

Abstract

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
• imiquimod
• immune response
• immunotherapy
• pharmacokinetics
• poly I:C
• resiquimod
• TLR agonist
• Toll-like receptor

Financial & competing interests disclosure

This work was supported by the following grants from the National Institute of Health: R01 CA138547 (Hailing Lu), P30 HL101321 (Gregory E Holt) and T32 AT000815 (Abbi L Engel). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.