Hematopoietic and pluripotent stem cells can be differentiated into T cells with potential clinical utility. Current approaches for in vitro T cell production rely on Notch signaling and artificial mimicry of thymic selection. However, these approaches result in unconventional or phenotypically aberrant T cells; which may lead to unpredictable behavior in clinical use. Thus, there exists a need for improved methods of generating conventional T cells in vitro from stem cells. Researchers at the National Cancer Institute (NCI) have developed a novel method for the in vitro differentiation of induced pluripotent stem cells (iPSCs) into induced pluripotent stem cell thymic emigrant (iTE) cells. Cells produced by this method are functionally equivalent to natural nave CD8+ T cells. The approach utilizes improved fetal thymic organ culture methodology to mature progenitor cells into conventional T cells in the presence of extrinsic Notch signaling. Cell culture conditions further provide for positive and negative selection to ensure proper maturation. This method produces conventional T cells that are suitable for clinical applications such adoptive cell therapy.

The NCI, Surgery Branch, is seeking statements of capability or interest from parties interested in licensing or collaborative research to further develop, evaluate, or commercialize this method of generating nave T cells from iPSCs.

Image: A visual allegory of the generation of iPSC-derived thymic emigrants (in red). Photo credit: Michael J. Kruhlak, Experimental Transplantation and Immunology Branch (ETIB)

CCR News: https://ccr.cancer.gov/news/article/stem-cell-technology-rejuvenates-can...

Development Stage: Pre-clinical (in vivo)

Related Invention(s): E-133-2017

Inventors:

Raul Vizcardo (NCI)more inventions...

Nicholas Klemen (NCI)more inventions...

Nicholas Restifo (NCI)more inventions...

Intellectual Property: Application No. 62/433,591 Application No. PCT/US2017/065986 Publications:Vizcardo, R, et al. Generation of tumor antigen-specific iPSC-derived thymic emigrants using a 3D thymic culture system. PMID 29562175 Collaboration Opportunity: Licensing and research collaboration

Licensing Contact: John Hewes, Ph.D. Email: John.Hewes@nih.gov Phone: 240-276-5515

OTT Reference No: E-250-2016 Updated: Dec 14, 2018

Originally posted here:
Methods of Producing Thymic Emigrants from Induced ...