Introduction

The Toll-like Receptor 4 (TLR4) is a key receptor of innate immunity cells that is activated by bacterial lipopolysaccharide.

Molecules that activate TLR4 (agonists) have a strong immunostimulating activity that can be exploited in the field of Vaccine Adjuvants and Cancer Immunotherapeutics.

This invention relates to new TLR4 agonists with a monosaccharide structure. These non-toxic molecules are able to induce the production of inflammatory cytokines in human and murine cells, and are active in stimulating antibody production in vaccination experiments in mice.

Technical features

The monophosphoryl lipid A (MPLA) is a TLR4 agonist approved by FDA for use as adjuvant in HPV and HCV vaccines. MPLA is obtained from the natural compound lipid A by controlled hydrolysis of phosphate, it is not chemically homogeneous.

Similarly to MPLA, the synthetic TLR4 agonists described in the patent, are able to stimulate innate immunity activation and antibodies production in mice. The molecules have a monosaccharide structure (compounds FP11 and FP18 in the Figure) and can be obtained higly pure by  chemical synthesis starting from unexpensive precursors.

The synthesis of molecules is easier than that of MPLA, and they have very low toxicity.

Possible Applications

• The molecules can be used in vaccine formulations as adjuvants;
• The immunostimulating properties and the capacity to induce cytokine production make these molecules promising candidate for Cancer immunotherpeutics.

Advantages

Compared to MPLA the molecules FP11 and FP18 present:

• Low toxicity;
• High chemical purity;
• High water solubility;
• The molecules are easily accessible through sustainable synthetic processes.