Chimeric antigen receptor and methods of use thereof
AssigneeThe Regents of the University of California
InventorsChia-Yung Wu, James Onuffer, Wendell A. Lim
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Abstract
The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.
Claims26
An isolated nucleic acid comprising a nucleotide sequence encoding a first polypeptide and a second polypeptide of a heterodimeric chimeric antigen receptor (CAR), wherein the first and the second polypeptides are two separate polypeptides, such that when present in a eukaryotic cell membrane, the CAR dimerizes in the presence of a small molecule dimerizer and an antigen to which the first polypeptide of the CAR binds to produce titratable activity, wherein:
- a) the first polypeptide comprises, in order from N-terminus to C-terminus:
- i) an antigen binding domain comprising an antigen-binding single-chain Fv (scFv);
- ii) a transmembrane domain;
- and
- iii) a first member of a dimerization pair;
- and
- b) the second polypeptide comprises, in order from N-terminus to C-terminus:
- i) a transmembrane domain;
- ii) a second member of the dimerization pair;
- and
- iii) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM), wherein the intracellular signaling domain provides signal transduction activity,
- wherein the second polypeptide does not comprise an antigen-binding domain,
- wherein the first polypeptide, the second polypeptide or both the first and second polypeptides comprise a costimulatory polypeptide interposed between the transmembrane domain and the member of the dimerization pair, and wherein the costimulatory polypeptide is selected from the group consisting of:
- a 4-1BB polypeptide, a CD28 polypeptide and an OX-40 polypeptide.
Dependencies are inferred from the claim text.