T CELL MODIFICATION
Improved compositions and methods for treating diseases, such as cancer, by providing a cell immunotherapy, wherein the cell immunotherapy is an immunomodulatory cell expressing an exogenous CD8 co-receptor and a modified T cell receptor (TCR) are provided. Also provided are polynucleotides, expression vectors, and immunomodulatory cells including the immunotherapy, as well as methods of generating said immunomodulatory cells.
1 . A population of modified T cells that present an exogenous CD8 co-receptor or fragment thereof, and a T cell receptor (TCR).
2 . A population of modified T cells of claim 1 wherein the CD8 co-receptor is CD8α.
3 . A population of modified T cells of claim 2 wherein the CD8 co-receptor comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 1.
4 . A population of modified T cells of claim 1 wherein the TCR is an affinity enhanced TCR.
5 . A population of modified T cells of claim 1 wherein the TCR is a NY-ESO-1 TCR.
6 . A population of modified T cells of claim 5 wherein the TCR comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 2.
7 . A population of modified T cells of claim 5 wherein the TCR comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 3.
8 . A nucleic acid construct comprising;
i. a first nucleotide sequence encoding a CD8 co-receptor for fragment thereof; and
ii. a second nucleotide sequence encoding a T cell receptor.
9 . A nucleic acid construct according to claim 8 wherein the CD8 co-receptor is CD8α.
10 . A nucleic acid construct according to claim 9 wherein the nucleotide sequence encoding CD8α comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO: 4.
11 . A nucleic acid construct of claim 8 wherein the TCR is an affinity enhanced TCR.
12 . A nucleic acid construct according to claim 8 wherein the TCR is a NY-ESO-1 TCR.
13 . A nucleic acid construct according to claim 12 wherein the TCR comprises a nucleic acid having at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NO: 5.
14 . A nucleic acid construct according to claim 12 wherein the TCR comprises a nucleic acid having at least 80% sequence identity to SEQ ID NO: 6.
15 . A vector comprising a nucleic acid construct according claim 8 .
16 . A vector according to claim 15 wherein the vector is a lentiviral vector.
17 . A population of T cells comprising a nucleic acid construct according to claim 8 .
18 . A pharmaceutical composition comprising a population of T cells according to claim 1 , and a pharmaceutically acceptable carrier.
19 . (canceled)
20 . A method for treating a subject afflicted with cancer, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition according to claim 18 .
21 . (canceled)
22 . A method of engineering a modified T cell comprising:
i. Providing a T cell;
ii. Introducing the vector of claim 15 into said T cell; and
iii. Expressing said vector in the T cell.