US 12,076,342 B2
Method for generating progenitor t cells from stem and/or progenitor cells and use of same
Peter W. Zandstra, Toronto (CA); and Shreya Shukla, Toronto (CA)
Assigned to THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO, Toronto (CA)
Appl. No. 16/091,266
Filed by THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO, Toronto (CA)
PCT Filed Apr. 7, 2017, PCT No. PCT/CA2017/050428
§ 371(c)(1), (2) Date Oct. 4, 2018,
PCT Pub. No. WO2017/173551, PCT Pub. Date Oct. 12, 2017.
Claims priority of provisional application 62/320,005, filed on Apr. 8, 2016.
Prior Publication US 2019/0142867 A1, May 16, 2019
Int. Cl. A61K 35/17 (2015.01); C12N 5/074 (2010.01); C12N 5/0783 (2010.01); C12N 5/0789 (2010.01); A61P 7/00 (2006.01); A61P 35/00 (2006.01)
CPC A61K 35/17 (2013.01) [C12N 5/0607 (2013.01); C12N 5/0636 (2013.01); C12N 5/0647 (2013.01); C12N 5/0696 (2013.01); A61P 7/00 (2018.01); A61P 35/00 (2018.01); C12N 2500/38 (2013.01); C12N 2500/99 (2013.01); C12N 2501/115 (2013.01); C12N 2501/125 (2013.01); C12N 2501/145 (2013.01); C12N 2501/155 (2013.01); C12N 2501/165 (2013.01); C12N 2501/2307 (2013.01); C12N 2501/25 (2013.01); C12N 2501/42 (2013.01); C12N 2501/58 (2013.01); C12N 2501/998 (2013.01); C12N 2502/1171 (2013.01); C12N 2533/52 (2013.01); C12N 2533/90 (2013.01)] 9 Claims
 
1. A method of generating progenitor T cells from stem and/or progenitor cells, the method comprising:
culturing a cell population comprising stem and/or progenitor cells in the presence of at least a portion of Notch ligand Delta-like-4 (DL4) and at least a portion of vascular adhesion molecule 1 (VCAM-1) under serum-free conditions in the absence of stromal or feeder cells,
wherein said culturing step increases the yield of progenitor T cells in said cell population as compared to progenitor T-cells cultured under serum-free conditions in the absence of stromal or feeder cells and not cultured in the presence of at least a portion of DL4 and at least a portion of VCAM-1, and
wherein said portion of DL4 comprises at least a signaling peptide of DL4, and wherein said portion of VCAM-1 comprises at least a signaling peptide of VCAM-1 and wherein the stem and/or progenitor stem cells are pluripotent stem cells or hematopoietic stem and progenitor cells.