Engineered T cell receptors and methods of use
This disclosure provides for engineered T cell Receptors (TCRs), cells comprising the TCRs, and methods of making and using the TCRs. The current disclosure relates to TCRs that specifically recognize gp100. Accordingly, aspects of the disclosure relate to an engineered T-cell Receptors (TCRs), nucleic acids encoding the TCRs, and cells comprising the nucleic acids and TCRs. Also provided are compositions comprising the cells, nucleic acids, or engineered TCRs of the disclosure, methods of making the cells and methods of using the embodiments of the disclosure for therapeutic treatments.
1 . An engineered T-cell Receptor (TCR) comprising a TCR alpha (TCR-a) polypeptide and a TCR beta (TCR-b) polypeptide, wherein the TCR-a polypeptide comprises a CDR1, CDR2, and CDR3 comprising the amino acid sequence of SEQ ID NOS: 1-3, respectively and the TCR-b polypeptide comprises a CDR1, CDR2, and CDR3 comprising the amino acid sequence of SEQ ID NOS: 6-8, respectively.
2 . The TCR of claim 1 , wherein the TCR-a polypeptide and TCR-b polypeptide are on the same polypeptide.
3 . A fusion protein comprising the TCR of claim 1 and a CD3 binding region.
4 . A nucleic acid(s) encoding the TCR of claim 1 .
5 . A nucleic acid vector comprising the nucleic acid(s) of claim 4 .
6 . A cell comprising the nucleic acid(s) of claim 4 .
7 . A composition comprising the cell of claim 6 .
8 . A method of making an engineered cell comprising transferring the nucleic acid of claim 4 into a cell.
9 . A method for treating melanoma in a subject comprising administering the composition of claim 7 to a subject in need thereof.
10 . The TCR of claim 1 , wherein the TCR-a polypeptide comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO:5 and the TCR-b polypeptide comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 10.
11 . The TCR of claim 1 , wherein the TCR-a polypeptide comprises the amino acid sequence of SEQ ID NO:5 and the TCR-b polypeptide comprises the amino acid sequence of SEQ ID NO:10.
12 . The TCR of claim 1 , wherein the TCR-a polypeptide comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO:4 and the TCR-b polypeptide comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 9.
13 . The TCR of claim 1 , wherein the TCR-a polypeptide comprises the amino acid sequence of SEQ ID NO:4 and the TCR-b polypeptide comprises the amino acid sequence of SEQ ID NO:9.
14 . The TCR of claim 2 , wherein the TCR-a polypeptide is amino-proximal to the TCR-b polypeptide.
15 . The TCR of claim 2 , wherein the TCR-b polypeptide is amino-proximal to the TCR-a polypeptide.
16 . The cell of claim 6 , wherein the cell comprises a stem cell, a progenitor cell, an immune cell, or a natural killer (NK) cell.
17 . The cell of claim 16 , wherein the cell comprises a hematopoietic stem or progenitor cell, a T cell, or an induced pluripotent stem cell (iPSC).
18 . The cell of claim 17 , wherein the cell is a T cell.
19 . The cell of claim 18 , wherein the T cell comprises an invariant NK T (INKT) cell, a gamma-delta T cell, or a regulatory T cell.
20 . The cell of claim 6 , wherein the cell is isolated from a cancer patient.
21 . The nucleic acid(s) of claim 4 , wherein the nucleic acid comprises a cDNA encoding the TCR-a and/or TCR-b genes.