In vitro assays with dendritic cells (DCs) show the ability of this agonist to activate dentritic cells as evidenced by secretion of IL-6, IL-12 and other pro-inflammatory cytokines. This agonist is specific for TLR4 and can not signal TLR4 negative cells. This agonist can function at 1-10 nM range. UCLA is now seeking commercial partners to further optimize this agonist in preparation for in vivo studies including determination of the minimum required peptide for activation.

INNOVATION:  Toll-like receptors (TLRs) are cell surface proteins of the innate immune system that are capable of recognizing pathogen-specific molecules. TLRs are expressed on several immune cells including DCs where it acts as a master regulatory switch and plays an important role in reversing the immune tolerant effects of T cells. TLR4 agonists have immunoregulatory applications such as adjuvants for vaccines, treatment of chronic viral infections, and cancer therapy. However, the best known TLR4 agonist, LPS, is toxic when used in humans.

POTENTIAL APPLICATIONS 

• Adjuvant to increase immunogenicity of any antigen in a vaccine
• Treatment for chronic viral infections (Hepatitis C, HPV)
• Cancer therapy using transduced agonist in patient cancer cells

ADVANTAGES

• Single recombinant peptide formulation results in highly specific TLR4 agonist
• Known safety profile of agonist, previously used in human clinical trials for alternate use
• Agonist has known target and mechanism of action

Reference: UCLA Case Nos. 2006-691, 2006-001