US 12,454,564 B2
Compositions and methods for T cell engineering
Xinxin Wang, Shanghai (CN); Tao Jin, Shanghai (CN); Chunhui Yang, Shanghai (CN); Zhongdong Shi, Shanghai (CN); Liping Liu, Shanghai (CN); Jing Sun, Shanghai (CN); Shuyi Qiu, Shanghai (CN); and Wei Cao, Shanghai (CN)
Assigned to Gracell Biotechnologies (Shanghai) Co., Ltd., Shanghai (CN); and Suzhou Gracell Biotechnologies Co., Ltd., Jiangsu (CN)
Filed by Gracell Biotechnologies (Shanghai) Co., Ltd., Shanghai (CN); and Suzhou Gracell Biotechnologies Co., Ltd., Jiangsu (CN)
Filed on Aug. 23, 2022, as Appl. No. 17/821,664.
Application 17/821,664 is a division of application No. 17/246,394, filed on Apr. 30, 2021, abandoned.
Application 17/246,394 is a continuation of application No. PCT/CN2019/114939, filed on Nov. 1, 2019.
Claims priority of application No. 201811297174.3 (CN), filed on Nov. 1, 2018; application No. 201811535338.1 (CN), filed on Dec. 14, 2018; application No. 201811549651.0 (CN), filed on Dec. 18, 2018; application No. 201910492882.0 (CN), filed on Jun. 6, 2019; and application No. PCT/CN2019/101651 (WO), filed on Aug. 20, 2019.
Prior Publication US 2023/0068085 A1, Mar. 2, 2023
Int. Cl. C07K 14/725 (2006.01); A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/42 (2025.01); A61K 40/50 (2025.01); A61P 35/00 (2006.01); C07K 14/705 (2006.01); C07K 14/71 (2006.01); C07K 16/28 (2006.01); C12N 5/0783 (2010.01); C12N 15/113 (2010.01); C12N 15/90 (2006.01); A61K 35/38 (2015.01); A61K 35/545 (2015.01); A61K 38/00 (2006.01)
CPC C07K 14/7051 (2013.01) [A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/4202 (2025.01); A61K 40/4204 (2025.01); A61K 40/421 (2025.01); A61K 40/4211 (2025.01); A61K 40/4215 (2025.01); A61P 35/00 (2018.01); C07K 14/70507 (2013.01); C07K 14/70596 (2013.01); C12N 5/0636 (2013.01); A61K 38/00 (2013.01); A61K 40/50 (2025.01); A61K 2239/23 (2023.05); A61K 2239/29 (2023.05); A61K 2239/31 (2023.05); A61K 2239/38 (2023.05); A61K 2239/48 (2023.05)] 11 Claims
 
1. A method for treating cancer in a human subject while reducing host-versus-graft (HvG) rejection by an innate T cell or NK cell in the human subject, the method comprising:
administering an engineered cytotoxic T cell to the human subject, wherein the engineered cytotoxic T cell comprises one or more chimeric antigen receptors (CARs) comprising:
a first antigen binding moiety exhibiting specific binding to CD7, wherein the first antigen binding moiety comprises a first scFv comprising a heavy chain variable domain (VH1) comprising the polypeptide sequence of SEQ ID NO: 91 and a light chain variable domain (VL1) comprising the polypeptide sequence of SEQ ID NO: 90; and
a second antigen binding moiety exhibiting specific binding to CD19, wherein the second antigen binding domain comprises a second scFv comprising a heavy chain variable domain (VH2) comprising the polypeptide sequence of SEQ ID NO: 88 and a light chain variable domain (VL2) comprising the polypeptide sequence of SEQ ID NO: 87,
wherein each CAR of the one or more CARs further comprises:
a hinge polypeptide, which is C-terminal to the first antigen binding moiety and the second antigen-binding moiety;
a transmembrane polypeptide, which is C-terminal to the hinge polypeptide; and
an intracellular signaling polypeptide comprising a signaling domain of CD3-zeta, which is C-terminal to the transmembrane polypeptide.