US 12,227,578 B2
Modulation of intestinal epithelial cell differentiation, maintenance and/or function through T cell action
Adam Haber, Cambridge, MA (US); Moshe Biton, Cambridge, MA (US); Rebecca H. Herbst, Cambridge, MA (US); Karthik Shekhar, Cambridge, MA (US); Christopher Smillie, Cambridge, MA (US); Orit Rozenblatt-Rosen, Cambridge, MA (US); Ramnik Xavier, Boston, MA (US); Aviv Regev, Cambridge, MA (US); Jose Ordovas-Montanes, Cambridge, MA (US); Alexander K. Shalek, Cambridge, MA (US); and Noga Rogel, Cambridge, MA (US)
Assigned to The Broad Institute, Inc., Cambridge, MA (US); Massachussetts Institute of Technology, Cambridge, MA (US); and The General Hospital Corporation, Boston, MA (US)
Appl. No. 16/348,911
Filed by The Broad Institute, Inc., Cambridge, MA (US); Massachusetts Institute of Technology, Cambridge, MA (US); and The General Hospital Corporation, Boston, MA (US)
PCT Filed Nov. 7, 2017, PCT No. PCT/US2017/060469
§ 371(c)(1), (2) Date May 10, 2019,
PCT Pub. No. WO2018/089386, PCT Pub. Date May 17, 2018.
Claims priority of provisional application 62/421,204, filed on Nov. 11, 2016.
Claims priority of provisional application 62/533,653, filed on Jul. 17, 2017.
Prior Publication US 2019/0263912 A1, Aug. 29, 2019
Int. Cl. G01N 33/50 (2006.01); A61K 35/17 (2015.01); A61P 1/04 (2006.01); A61P 1/14 (2006.01); A61P 31/04 (2006.01); A61P 33/00 (2006.01); C07K 14/47 (2006.01); C07K 14/52 (2006.01); C07K 14/71 (2006.01); C07K 16/28 (2006.01); C12N 5/071 (2010.01); C12N 5/0783 (2010.01); G01N 33/569 (2006.01)
CPC C07K 16/2833 (2013.01) [A61K 35/17 (2013.01); A61P 1/04 (2018.01); A61P 1/14 (2018.01); A61P 31/04 (2018.01); A61P 33/00 (2018.01); C07K 14/47 (2013.01); C07K 14/52 (2013.01); C07K 14/71 (2013.01); C12N 5/0636 (2013.01); C12N 5/0637 (2013.01); C12N 5/0679 (2013.01); G01N 33/5044 (2013.01); G01N 33/56966 (2013.01); G01N 33/56972 (2013.01); G01N 2800/26 (2013.01)] 18 Claims
 
1. A method of modulating intestinal epithelial cell composition in an intestinal organoid culture comprising intestinal epithelial cells, the method comprising:
co-culturing the intestinal organoid with Th1, Th2, Th17, or regulatory T (Treg) cells in an amount sufficient to modify the intestinal epithelial cell composition, whereby the Th1, Th2, Th17, or Treg cells directly influence intestinal epithelial cell proliferation, differentiation, and/or maintenance; and
detecting intestinal epithelial cells after co-culturing the intestinal organoid culture with Th1, Th2, Th17, or regulatory T (Treg) cells, whereby the intestinal epithelial cell composition is monitored, and wherein detecting intestinal epithelial cells comprises performing single cell RNA-seq (scRNA-seq) on the intestinal organoid culture.