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

Summary
The thymus is the only organ capable of producing conventional, mature T cells; a crucial part of the adaptive immune system. However, its efficiency and function are progressively reduced as we age, leading to a compromised immune system in the elderly. Moreover, production of T cells with specific receptors is an important concern for cancer immunotherapy. Current in vitro methods produce immature T cells that are not useful for therapy. Researchers at the National Cancer Institute (NCI) have generated an autologous thymic organoid from human pluripotent stem cells to address this problem. The organoid can be used to develop clinical applications such as production of autologous T and natural killer T (NKT) cells and reconstitution of the adaptive immune system. NCI is seeking licensees for the thymic organoid and the method of its generation to be used in a variety of clinical applications.
NIH Reference Number
E-133-2017
Product Type
Keywords
  • Organoid, Organogenesis, Thymus, Pluripotent Stem Cells, T Cells, Natural Killer T Cells, NKT, Immunocompromised, Aging, Immunotherapy, Vizcardo
Collaboration Opportunity
This invention is available for licensing.
Contact
Description of Technology

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.

Potential 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
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 
Inventor(s)

Raul Vizcardo Ph.D. (NCI), Nicholas Restifo M.D. (NCI)

Development Stage
Publications

Vizcardo R, et al. Generation of tumor antigen-specific iPSC-derived thymic emigrants using a 3D thymic culture system.  [PMID 29562175]

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/560,908 , Filed 20 Sep 2017
  • PCT: PCT Application Number PCT/US2018/051625 , Filed 19 Sep 2018
Therapeutic Area
Updated
Wednesday, September 18, 2019