FRED HUTCHINSON CANCER RESEARCH CENTER;SEATTLE CHILDREN’S HOSPITAL DBA SEATTLE CHILDREN’S RESEARCH INSTITUTE
发明人:
Jensen, Michael,Riddell, Stanley,Hudecek, Michael
申请号:
NZ73863613
公开号:
NZ738636A
申请日:
2013.08.20
申请国别(地区):
NZ
年份:
2020
代理人:
摘要:
The invention relates to a nucleic acid encoding a chimeric receptor, the chimeric receptor comprising: (a) an extracellular domain consisting of: an extracellular ligand binding domain consisting of a single chain variable fragment (scFv) that binds to a CD19, wherein the scFv comprises a variable light chain (VL) domain comprising a CDRL1, a CDRL2, and a CDRL3 of the amino acid sequence encoded by SEQ ID NO:3, and a variable heavy chain (VH) domain comprising a CDRH1, a CDRH2, and a CDRH3 of the amino acid sequence encoded by SEQ ID NO:3; and an extracellular polypeptide spacer that is about 15 amino acids or less in length and comprises an amino acid sequence of X1PPX2P, wherein X1 is a cysteine, glycine, or arginine and X2 is a cysteine or a threonine (SEQ ID NO:1); (b) a transmembrane domain; and (c) an intracellular signaling domain that comprises a CD3ζ signaling domain and a costimulatory domain. Also provided is a nucleic acid encoding a chimeric receptor, the nucleic acid comprising: (a) a polynucleotide encoding a single chain variable fragment (scFv) that binds to CD19, wherein the scFv comprises: a variable light chain (VL) domain comprising a VL domain present in the amino acid sequence encoded by SEQ ID NO:3, and a variable heavy chain (VH) domain comprising a VH domain present in the amino acid sequence encoded by SEQ ID NO:3; or the amino acid sequence encoded by SEQ ID NO:3; (b) a polynucleotide encoding a transmembrane domain; (c) a polynucleotide encoding a polypeptide spacer located between the scFv and the transmembrane domain, wherein the polypeptide spacer is about 15 amino acids or less in length and comprises an amino acid sequence of X1PPX2P, wherein X1 is a cysteine, glycine, or arginine and X2 is a cysteine or a threonine (SEQ ID NO:1); and (d) a polynucleotide encoding an intracellular signaling domain that comprises a CD3ζ signaling domain and a costimulatory domain. Also provided are vectors that include the nucleic acids and methods