Toll-like receptor modulators: a patent review (2006-2010)

Shaherin Basith, Balachandran Manavalan, Gwang Lee, Sang Geon Kim, Sangdun Choi
Expert Opinion on Therapeutic Patents 2011, 21 (6): 927-44

INTRODUCTION: The immune response is mediated via two parallel immune components, innate and adaptive, whose effector functions are highly integrated and coordinated for the protection of the human body against invading pathogens and transformed cells. The discovery of pathogen recognition receptors (PRRs), most notably toll-like receptors (TLRs), in innate immunity has evoked increased interest in the therapeutic handling of the innate immune system. TLRs are germ line-encoded receptors that play a potent role in the recognition of a diverse variety of ligands ranging from hydrophilic nucleic acids to lipopolysaccharide (LPS) or peptidoglycan (PGN) structures in pathogens.

AREAS COVERED: This review discusses recent updates (2006-2010) in completed, ongoing and planned clinical trials of TLR immunomodulator-based therapies for the treatment of infectious diseases, inflammatory disorders and cancer.

EXPERT OPINION: Since the discovery of human TLRs, modulating immune responses using TLR agonists or antagonists for therapeutic purposes has provoked intense activity in the pharmaceutical industry. The ability of TLRs to initiate and propagate inflammation makes them attractive therapeutic targets. We are now at the stage of evaluating such molecules in human diseases. Additionally, there is also extensive literature available on TLRs in diseased states. These data provide a basis for the identification of novel immunomodulators (agonists and antagonists) for the therapeutic targeting of TLRs.

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