New immunomodulatory glycolipids

New tiourea- and urea-based glycolipids with immunomodulatory activity. The compounds are Mincle agonist and have shown in vitro and in vivo immunostimulant activity. They can be used as vacine adjuvants, in the modulation of the immune response and in the treatment of infectious disease or cancer.

Market need: The macrophage-inducible C-type lectin (Mincle) is a transmembrane C-type lectin receptor (CLR) expressed on immune system cells such as macrophages and dendritic cells. The activation of Mincle initiates a signaling cascade leading to an imunostimulating effect
Over the past decade, many glycolipids have been synthesized as Mincle activators. However, most of them are too far reactogenic or toxic so cannot be used as therapeutic agents. Alternative Mincle agonists are needed to advance new vaccine adjuvants and therapeutics in the areas of infectious diseases, as well as autoimmunity and cancer.

Proposed solution: New carbohydrate derivatives behaving as agonists of the Mincle receptor in immune system cells have been identified using a reporter T-cell hybridoma that expresses Mincle and FcRg as well as GFP (green fluorescent protein) under the control of the NFAT transcription factor.
The immunostimulant function of the compounds has been shown in vitro in different human and mouse cells.
Moreover, the ability of compounds to function as an adjuvant was assessed in a mouse model in vivo.

Competitive advantages

The new compounds can elicit and inflammatory response both in vitro and in vivo and they represent a new class of Th1/Th17-inducing adjuvants.
The incorporation of tiourea and urea connectors between de carbohydrate and the lipid moieties enables efficient and scalable preparation protocols.
The compounds can be used as vaccine adjuvants, or in the modulation of immune response in a subject, or in the treatment of infectious diseases or in the treatment of cancer.