	US 11,938,153 B2
	Methods of treating T cell exhaustion by inhibiting or modulating T cell receptor signaling
Rachel Lynn, Stanford, CA (US); Crystal Mackall, Stanford, CA (US); Tom J. Wandless, Stanford, CA (US); and Evan Weber, Stanford, CA (US)
Assigned to The Board of Trustees of the Leland Stanford Junior University, Stanford, CA (US)
Appl. No. 16/499,760
Filed by THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, Stanford, CA (US)
PCT Filed Mar. 30, 2018, PCT No. PCT/US2018/025459 § 371(c)(1), (2) Date Sep. 30, 2019, PCT Pub. No. WO2018/083888, PCT Pub. Date Oct. 4, 2018.
Claims priority of provisional application 62/479,930, filed on Mar. 31, 2017.
Prior Publication US 2021/0032363 A1, Feb. 4, 2021
Int. Cl. A61K 35/17 (2015.01); A61K 31/5025 (2006.01); A61K 31/506 (2006.01); A61P 35/00 (2006.01); C07K 14/705 (2006.01); C07K 14/725 (2006.01); C07K 16/30 (2006.01); C12N 5/0783 (2010.01); C12N 9/90 (2006.01)

CPC A61K 35/17 (2013.01) [A61K 31/5025 (2013.01); A61K 31/506 (2013.01); A61P 35/00 (2018.01); C07K 14/7051 (2013.01); C07K 14/70521 (2013.01); C07K 14/70578 (2013.01); C07K 16/3084 (2013.01); C12N 5/0636 (2013.01); C12N 9/90 (2013.01); C07K 2317/622 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/33 (2013.01); C12N 2501/727 (2013.01); C12N 2510/00 (2013.01)]

14 Claims

1. A genetically modified T cell comprising an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises:

a) an extracellular domain comprising an antigen-binding region;

b) a transmembrane domain;

c) an intracellular signaling domain; and

d) a regulatable destabilization domain (RDD), wherein the RDD comprises a dihydrofolate reductase destabilization domain (DHFR DD) or an FK506 binding protein 12 (FKBP) destabilization domain (FKBP DD).