In May 2005, Cytheris acquired an exclusive worldwide license to a family of natural killer T (NKT) cell ligands from New York University, the Aaron Diamond AIDS Research Center and the City University of New York. Under the terms of the agreement, Cytheris received development and marketing rights for a new family of molecules in the field of immuno-modulation resulting from research carried out by these three leading academic institutions.

The family of new molecules is made up of highly potent and specific ligands that activate NKT and dendritic cells inducing the secondary release of both IL-12 and IFNy. NKT cell biology has emerged as a new field of research at the frontier between innate and adaptive immunity, providing a powerful model to study fundamental aspects of the cell and structural biology of glycolipid trafficking, processing, and recognition.

Over the past 10 years NKT cells have been the focus of much attention. The functions of these unique lymphocytes, characterized by the concomitant expression of T- and NK-cell markers and thus termed NKT cells, have been implicated in many diverse aspects of immunity, including regulation of autoimmune disorders, control of tumor growth and spread, and defense against a number of pathogens. These cells have the capacity, either constitutively or post activation, to promote an array of immunoregulatory responses. They rapidly produce many cytokines after stimulation and thus influence diverse immune responses and pathogenic processes.

NKT cells, considered a critical hinge between the innate and adaptive arms of the immune system, play a pivotal role in prompting many infection- and disease- fighting immune cells to act against pathogens and cancer. Whereas, dendritic cells are at the heart of the immune system's operations in processing and presenting antigens to the immune system, the interaction of NKT cells with dendritic cells results in the production of many immune-enhancing cytokines acting on immune system cells. These cytokines can expand or differentiate, or develop into, helpers or killers focused on removing an antigen.

The involvement of NKT cells in viral immune-surveillance and, when activated, their ability to induce protection against pathogens makes them a highly attractive clinical target.

Other uses of these ligands include potential as stand-alone agent and as a vaccine adjuvant. The proof of concept has been validated in animal models and preliminary results indicate high potency at very low dosage, confirming the high specificity of these products. 

Acronyms and Definitions

CD1: A family of MHC-like molecules that specialize in presenting lipid antigens to T lymphocytes.

α-glycuronylceramides: Glycolipids that substitute for LPS in the cell wall of Gram-negative, LPS-negative bacteria such as Sphingomonas.

Natural killer T cell: A T cell expressing a CD1d-restricted, lipid-specific T cell receptor combining a canonical Vα14-Jα18 α chain with a variable Vβ8, -7, or -2 β chain in mouse or with Vβ11 in human.