T-cell receptors targeting egfr and methods of use thereof
AssigneeBoard of Regents, The University of Texas System
InventorsAlexandre Reuben, Minying Zhang, John Victor Heymach, Gregory A. Lizee, Peixin Jiang
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Abstract
The present disclosure provides T-cell receptors comprising an antigen binding variable region that specifically binds an antigenic peptide derived from EGFR L858R. The present disclosure, further provides activated or engineered T-cells comprising the T-cell receptors of the disclosure, and methods of making and using these T-cell receptors. Aspects of the disclosure further relate to a polypeptide comprising an antigen binding variable region comprising a CDR3 region of the disclosure.
Claims66
A recombinant polynucleotide molecule comprising a nucleotide sequence that encodes an antigen binding variable region comprising a CDR3 region, wherein said CDR3 region comprises the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:11.
A recombinant polynucleotide molecule comprising a nucleotide sequence that encodes an antigen binding variable region comprising a CDR3 region, wherein:
- a) said CDR3 region consists essentially of the amino acid sequence of SEQ ID NO:
- 7;
- b) said CDR3 region comprises the amino acid sequence of SEQ ID NO:7, and wherein said antigen binding variable region comprises an amino acid sequence having at least about 85% sequence identity to SEQ ID NO:8;
- c) said CDR3 region comprises the amino acid sequence of SEQ ID NO:7, and wherein said antigen binding variable region further comprises an amino acid sequence selected from the group consisting of SEQ ID NO:5 or SEQ ID NO:6;
- or
- d) said CDR3 region comprising the amino acid sequence of SEQ ID NO:15.
A composition comprising a polypeptide, wherein said polypeptide comprises an antigen binding variable region comprising a CDR3 region, wherein:
- a) said CDR3 region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:11, or SEQ ID NO:15;
- b) said CDR3 region consists essentially of the amino acid sequence of SEQ ID NO:
- 7;
- c) said CDR3 region comprises the amino acid sequence of SEQ ID NO:7, and wherein said antigen binding variable region comprises an amino acid sequence having at least about 85% sequence identity to SEQ ID NO:8;
- or
- d) said CDR3 region comprises the amino acid sequence of SEQ ID NO:7, and wherein said antigen binding variable region further comprises the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6.
A method for treating cancer, the method comprising administering a population of activated T-cells that comprise a polypeptide to a patient in need thereof, wherein said polypeptide comprises an antigen binding variable region comprising a CDR3 region, and wherein:
- a) said CDR3 region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:11, or SEQ ID NO:15;
- b) said CDR3 region consists essentially of the amino acid sequence of SEQ ID NO:
- 7;
- c) said CDR3 region comprises the amino acid sequence of SEQ ID NO:7, and wherein said antigen binding variable region comprises an amino acid sequence having at least about 85% sequence identity to SEQ ID NO:8;
- or
- d) said CDR3 region comprises the amino acid sequence of SEQ ID NO:7, and wherein said antigen binding variable region further comprises the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6.
A recombinant T-cell receptor comprising a TCRβ chain variable region and a TCRα chain variable region wherein:
- a) the TCRβ chain variable region comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:3, and further comprises an amino acid sequence having at least about 85%, about 90%, or about 95% sequence identity to the amino acid sequence of SEQ ID NO:4, and wherein the TCRα chain variable region comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:7, and further comprises an amino acid sequence having at least about 85%, about 90%, or about 95% sequence identity to the amino acid sequence of SEQ ID NO:8;
- or
- b) the TCRβ chain variable region comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:11, and further comprises an amino acid sequence having at least about 85%, about 90%, or about 95% sequence identity to the amino acid sequence of SEQ ID NO:12, and wherein the TCRα chain variable region comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:15, and further comprises an amino acid sequence having at least about 85%, about 90%, or about 95% sequence identity to the amino acid sequence of SEQ ID NO:16.
A composition comprising a T-cell receptor comprising a TCRβ chain variable region and a TCRα chain variable region, wherein:
- a) the TCRβ chain variable region comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:3, and further comprises an amino acid sequence having at least about 85%, about 90%, or about 95% sequence identity to the amino acid sequence of SEQ ID NO:4, and wherein the TCRα chain variable region comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:7, and further comprises an amino acid sequence having at least about 85%, about 90%, or about 95% sequence identity to the amino acid sequence of SEQ ID NO:8;
- or
- b) the TCRβ chain variable region comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:11, and further comprises an amino acid sequence having at least about 85%, about 90%, or about 95% sequence identity to the amino acid sequence of SEQ ID NO:12, and wherein the TCRα chain variable region comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO:15, and further comprises an amino acid sequence having at least about 85%, about 90%, or about 95% sequence identity to the amino acid sequence of SEQ ID NO:16.
A bi-specific T-cell engager comprising a TCRβ chain variable region and a TCRα chain variable region, wherein:
- a) the TCRβ chain variable region comprises a CDR3β region comprising the amino acid sequence of SEQ ID NO:3, and wherein the TCRα chain variable region comprises a CDR3α region comprising the amino acid sequence of SEQ ID NO:7;
- or
- b) the TCRβ chain variable region comprises a CDR3β region comprising the amino acid sequence of SEQ ID NO:11, and wherein the TCRα chain variable region comprises a CDR3α region comprising the amino acid sequence of SEQ ID NO:15.
Dependencies are inferred from the claim text.