US 12,281,164 B2
Genetically engineered dual-targeting chimeric antigen receptor and use thereof
Yongsheng Wang, Sichuan (CN); Qizhi Ma, Sichuan (CN); Dan Li, Sichuan (CN); and Qiyu Yang, Sichuan (CN)
Assigned to WEST CHINA HOSPITAL, SICHUAN UNIVERSITY, Sichuan (CN)
Appl. No. 17/442,720
Filed by WEST CHINA HOSPITAL, SICHUAN UNIVERSITY, Sichuan (CN)
PCT Filed Nov. 12, 2019, PCT No. PCT/CN2019/117601
§ 371(c)(1), (2) Date Sep. 24, 2021,
PCT Pub. No. WO2020/125277, PCT Pub. Date Jun. 25, 2020.
Claims priority of application No. 201811567513.5 (CN), filed on Dec. 20, 2018.
Prior Publication US 2022/0185893 A1, Jun. 16, 2022
Int. Cl. C07K 16/00 (2006.01); A61P 35/04 (2006.01); C07K 16/28 (2006.01); C07K 16/30 (2006.01); C07K 16/32 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/2827 (2013.01) [A61P 35/04 (2018.01); C07K 16/2863 (2013.01); C07K 16/30 (2013.01); C07K 16/32 (2013.01); A61K 2039/507 (2013.01); C07K 2317/622 (2013.01); C07K 2319/02 (2013.01); C07K 2319/03 (2013.01); C07K 2319/33 (2013.01); C07K 2319/50 (2013.01)] 13 Claims
 
1. A genetically engineered dual-targeting chimeric antigen receptor, comprising:
(a) a chimeric antigen receptor 1 comprising:
(1) an scFv antibody of human HER2, a CD28 transmembrane domain and a CD3ζ binding domain, which has the amino acid sequence shown in SEQ ID NO: 5 and/or is encoded by the nucleotide sequence shown in SEQ ID NO: 6; or
(ii) an scFv antibody of human VEGFR1, a CD28 transmembrane domain and a CD3ζ binding domain, which has the amino acid sequence shown in SEQ ID NO: 3 and/or is encoded by the nucleotide sequence shown in SEQ ID NO: 4;
(b) a chimeric antigen receptor 2 capable of recognizing PD-L1, which comprises a scFv antibody of human PD-L1, a CD8 transmembrane domain and a 4-1BB costimulatory molecular peptide fragment, and has the amino acid sequence shown in SEQ ID NO: 1 and/or is encoded by the nucleotide sequence shown in SEQ ID NO: 2; and
(c) a linker peptide linking the chimeric antigen receptor 1 with the chimeric antigen receptor 2.