Engineered t cell receptors and methods of use
View Patent ↗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 epitope(s) from tumor antigen COL6A3. 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-a polypeptide and a TCR-b polypeptide, wherein the TCR-a polypeptide comprises a CDR1 comprising the amino acid sequence of SEQ ID NO:6, a CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a CDR3 comprising an amino acid sequence of SEQ ID NO:8, and the TCR-b polypeptide comprises a CDR1 comprising the amino acid sequence of SEQ ID NO: 12, a CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and a CDR3 comprising an amino acid sequence of SEQ ID NO: 14.
2 . A fusion protein comprising the TCR of claim 1 and a CD3 binding region.
3 . One or more nucleic acids encoding the TCR of claim 1 .
4 . A nucleic acid vector comprising the one or more nucleic acids of claim 3 .
5 . An isolated cell comprising the one or more nucleic acids of claim 3 .
6 . A composition comprising the one or more nucleic acids of claim 3 .
7 . A method for treating cancer in a subject comprising administering the isolated cell of claim 5 to a subject in need thereof.
8 . The TCR of claim 1 , wherein the TCR-a polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO:4 and the TCR-b polypeptide comprises an amino acid sequence with at least 90% sequence identity to SEQ ID NO: 10.
9 . The TCR of claim 8 , 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: 10.
10 . The TCR of claim 1 , wherein the TCR-a polypeptide is amino-proximal to the TCR-b polypeptide.
11 . The TCR of claim 1 , wherein the TCR-b polypeptide is amino-proximal to the TCR-a polypeptide.
12 . The isolated cell of claim 5 , wherein the isolated cell comprises a hematopoietic stem or progenitor cell, a T cell, or an induced pluripotent stem cell (iPSC).
13 . The isolated cell of claim 12 , wherein the isolated cell comprises an invariant NK T (INKT) cell, a gamma-delta T cell, or a regulatory T cell.
14 . The cell of claim 5 , wherein the isolated cell is isolated from a cancer patient.
15 . The one or more nucleic acids of claim 3 , encoding the TCR-a polypeptide and the TCR-b polypeptide in a single nucleic acid.
16 . The engineered TCR of claim 1 , wherein the TCR is a single chain TCR.