TLR Agonists Emerge as Potential New Partner for Checkpoint Inhibitors

Jane De Lartigue, PhD
Published: Tuesday, May 14, 2019
Toll-like receptors (TLRs), a group of proteins that are components of innate immunity, are emerging as promising targets in a new wave of immunotherapies under development.


These first responders of the immune system help lay the groundwork for optimal activation of the adaptive immune response. Thus far, TLR agonists have had limited clinical success, partly due to the seemingly duplicitous role that many TLRs play in cancer.

Development efforts are far from over, however, and a greater understanding of the complexities of TLR signaling in cancer, combined with novel drug design, has yielded a growing number of investigational drugs. Particularly noteworthy are the new generation of TLR9 agonists, whose use could help to establish an ideal backdrop for optimal activation of T cell–based immunotherapies. Ongoing clinical trials have demonstrated exciting activity for TLR9 agonists combined with immune checkpoint inhibitors (ICIs).

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