T cell receptors specific for mesothelin and their use in immunotherapy
AssigneesFred Hutchinson Cancer Center, Juno Therapeutics, Inc.
InventorsThomas M. SCHMITT, Aude G. CHAPUIS, Philip D. GREENBERG
Life of this patent
Estimating the term…
Abstract
Binding proteins specific for Msln20-28 or Msln530-538 peptides are provided herein. Polynucleotides encoding the binding proteins, as well as compositions and recombinant host cells comprising the binding proteins or polynucleotides are also provided. The compositions and recombinant host cells may be used to treat a subject having mesothelioma, pancreatic cancer, ovarian cancer, lung cancer, a cancer wherein an Msln20-28 peptide is expressed on a tumor cell of the cancer, or a cancer wherein an Msln530-538 peptide is expressed on a tumor cell of the cancer.
Claims97
A binding protein comprising a T cell receptor (TCR) α-chain variable domain (Vα) and a TCR β-chain variable domain (Vβ), wherein:
- (a) the Vα comprises the CDR3 amino acid sequence set forth in SEQ ID NO:39 or 37, and the Vβ optionally comprises an amino acid sequence having at least about 85% identity to the amino acid sequence set forth in SEQ ID NO:101 or 99;
- (b) the Vβ comprises the CDR3 amino acid sequence set forth in SEQ ID NO:40 or SEQ ID NO:38, and the Vα optionally comprises an amino acid sequence having at least about 85% identity to the amino acid sequence set forth in SEQ ID NO:102 or 100;
- and/or
- (c) the Vα comprises the CDR3 amino acid sequence set forth in SEQ ID NO:39 or 37, and the Vβ comprises the CDR3 amino acid sequence set forth in SEQ ID NO:40 or 38,
- wherein the binding protein is capable of specifically binding to a mesothelin (Msln) peptide:HLA complex.
A binding protein comprising a T cell receptor (TCR) α-chain variable domain (Vα) and a TCR β-chain variable domain (Vβ), wherein:
- (a) the Vα comprises the CDR3 amino acid sequence set forth in SEQ ID NO:33 or 35, and the Vβ optionally comprises an amino acid sequence having at least about 85% identity to the amino acid sequence set forth in SEQ ID NO:95 or 97;
- (b) the Vβ comprises the CDR3 amino acid sequence set forth in SEQ ID NO:
- 34 or 36, and the Vα optionally comprises an amino acid sequence having at least about 85% identity to the amino acid sequence set forth in SEQ ID NO:96 or 98;
- and/or
- (c) the Vα comprises the CDR3 amino acid sequence shown in SEQ ID NO:33 or 35, and the Vβ comprises the CDR3 amino acid sequence shown in SEQ ID NO:40 or 38,
- wherein the binding protein is capable of specifically binding to a mesothelin (Msln) peptide:HLA complex.
An isolated polynucleotide that encodes a binding protein that is capable of specifically binding to a SEQ ID NO:32:HLA-A:02*01 complex, wherein the polynucleotide comprises or consists of the polynucleotide sequence set forth in SEQ ID NO:120.
Dependencies are inferred from the claim text.