The future of toll-like receptor therapeutics.

Since the discovery of human TLRs, manipulating the activity of these receptors to modulate immune responses for therapeutic purposes has initiated intense activity in the pharmaceutical industry. The focus of these activities has been largely in the areas of infectious diseases, cancer, allergic diseases and vaccine adjuvants. Although initial clinical trials for infectious diseases and cancer showed early promise, subsequent longer-term trials have been disappointing and more research is required to find dosing regimes that balance efficacy with acceptable side-effect profiles. As only a small number of doses are given, TLR agonists as vaccine adjuvants appear to hold greater potential and have less safety concerns than for other applications. Several innovative strategies for using TLR agonists in vaccine development are currently being pursued, and these are discussed in more detail in this review.