US 11,866,494 B2
CAR T therapy through uses of co-stimulation
Zhiyuan Cao, Shanghai (CN); Chengfei Pu, Shanghai (CN); Lei Xiao, Shanghai (CN); and Zhao Wu, Shanghai (CN)
Assigned to Innovative Cellular Therapeutics Holdings, Ltd., George Town (KY)
Filed by Innovative Cellular Therapeutics Co., Ltd., Grand Cayman (KY)
Filed on Aug. 27, 2019, as Appl. No. 16/552,521.
Claims priority of provisional application 62/725,967, filed on Aug. 31, 2018.
Prior Publication US 2020/0071400 A1, Mar. 5, 2020
Int. Cl. C07K 14/725 (2006.01); C12N 5/0783 (2010.01); C07K 16/30 (2006.01); A61K 39/395 (2006.01); A61K 35/17 (2015.01); A61P 35/00 (2006.01); C07K 16/28 (2006.01); C07K 14/705 (2006.01); A61K 38/00 (2006.01)
CPC C07K 16/2803 (2013.01) [A61K 35/17 (2013.01); C07K 14/7051 (2013.01); C07K 14/70521 (2013.01); C07K 14/70532 (2013.01); C07K 14/70578 (2013.01); C12N 5/0636 (2013.01); A61K 38/00 (2013.01); C07K 2317/24 (2013.01); C07K 2317/55 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/76 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/30 (2013.01); C07K 2319/33 (2013.01); C12N 2510/00 (2013.01)] 9 Claims
 
1. A modified cell comprising a first nucleic acid encoding a chimeric antigen receptor (CAR) and a second nucleic acid encoding an agent binding a first co-stimulatory molecule,
wherein the CAR comprises an extracellular domain, a transmembrane domain, and an intracellular domain, the extracellular domain binds an antigen, and the intracellular domain comprises an intracellular domain of a first co-stimulatory molecule and a second co-stimulatory molecule,
wherein the first co-stimulatory molecule is GITR, and the second co-stimulatory molecule is 4-1BB, and the agent binding the first co-stimulatory molecule is glucocorticoid-induced TNFR-related protein ligand (GITRL), and
wherein the modified cell comprises a nucleic acid encoding the amino acid sequences SEQ ID NOs: 1, 2, 3, 5, 4, and 8 in 5′ to 3′ order.