Chimeric receptors with 4-1BB stimulatory signaling domain
AssigneeSt. Jude Children's Research Hospital
InventorsDario Campana, Chihaya Imai
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Abstract
The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.
Claims10
A chimeric antigen receptor comprising:
- (a) an extracellular ligand-binding domain comprising an anti-CD19 single chain variable fragment (scFv) domain;
- (b) a transmembrane domain;
- and (c) a cytoplasmic domain comprising a 4-1BB signaling domain and a CD3ζ signaling domain wherein the CD3ζ signaling domain comprises the amino acid sequence of SEQ ID No. 18.
A method of enhancing a T lymphocyte or an NK cell activity in a mammal comprising introducing into the mammal a T lymphocyte or NK cell, which T lymphocyte or NK cell comprises a chimeric receptor comprising:
- (a) an extracellular ligand- binding domain comprising an anti-CD19 single chain variable fragment (scFv) domain, (b) a hinge and transmembrane domain, and (c) a cytoplasmic domain comprising a 4-1BB signaling domain and a CD3ζ signaling domain comprising the amino acid sequence of SEQ ID No. 18.
A method for treating a mammal suffering from cancer comprising introducing into the mammal a T lymphocyte or an NK cell, which T lymphocyte or NK cell comprises a chimeric receptor comprising:
- (a) an extracellular ligand-binding domain comprising an anti-CD19 scFv domain;
- (b) a hinge region and transmembrane domain of CD8a;
- and (c) a cytoplasmic domain comprising a signaling domain of 4-1BB and a CD3ζ signaling domain comprising the amino acid sequence of SEQ ID No. 18.
A method for stimulating a T cell-mediated immune response to a target cell population or tissue in a mammal comprising administering to a mammal an effective amount of a cell genetically modified to express a chimeric antigen receptor (CAR), said CAR comprising:
- a) an extracellular ligand-binding domain comprising an anti-CD19 single chain variable fragment (scFv) domain, (b) a hinge and transmembrane domain, and (c) a cytoplasmic domain comprising a 4-1BB signaling domain and a CD3ζ signaling domain comprising the amino acid sequence of SEQ ID No. 18.
A method of providing an anti-tumor immunity in a mammal, the method comprising administering to the mammal an effective amount of a cell genetically modified to express a CAR, said CAR comprising:
- a) an extracellular ligand-binding domain comprising an anti-CD19 single chain variable fragment (scFv) domain, (b) a hinge and transmembrane domain, and (c) a cytoplasmic domain comprising a 4-1BB signaling domain and a CD3ζ signaling domain comprising the amino acid sequence of SEQ ID No. 18.
Dependencies are inferred from the claim text.