In vitro Generation of an Autologous Thymic Organoid from Human Pluripotent Stem Cells

The thymus is an integral part of the adaptive immune system as it generates T cells. Its function diminishes rapidly as the body ages, leading to a compromise of the immune system in the elderly. Reconstitution of adaptive immunity through mass production of different T cell types is therefore a therapeutic need in immunocompromised populations. Furthermore, production of T cells with specific receptors targeting cancer cells is an important cancer immunotherapy approach. However, current in vitro methods are not efficient in producing conventional CD4 or CD8 positive T cells, as they result in production of immature, CD4 and CD8 double positive T cells which are not useful for therapy. This problem may be solved through a three-dimensional cell culture system mimicking the human thymus.

Researchers at the National Cancer Institute (NCI) have developed a novel approach to generate autologous thymic organoids from human pluripotent stem cells. These organoids possess many features of a physiological human thymus and form structures resembling organized thymic tissue. As such, they are very promising candidates for production of therapeutic T cells and other cells of the adaptive immune system (e.g., natural killer cells).

The NCI is seeking statements of capability or interest from parties interested in licensing this invention to further develop, evaluate, or commercialize this method of generating thymic organoids for production of adaptive immune system cells.

Competitive Advantages:

• Three dimensional, fully human culture system produces an organoid which mimics the physiological properties of the thymus
• The thymic organoid form structures resembling organized thymic tissue
• The system can be adapted for mass production 

Commercial Applications:

• Regeneration of the adaptive immune system in immunocompromised and/or the elderly population
• Organoid technology as a disease model, and to predict the outcome of drug responses in vitro 
• In vitro generation of T and natural killer T (NKT) cells with specific receptors to target cancer cells
• Treatment of anemias, autoimmune disorders, rare blood diseases, and infections