CHIMERIC ANTIGEN RECEPTORS TARGETING CD-19
The invention is directed to a chimeric antigen receptor (CAR) directed against CD19, which comprises an amino acid sequence of any one of SEQ ID NO: 1-SEQ ID NO: 13. The invention also provides T-cells expressing the CAR and methods for destroying malignant B-cells.
1 . A population of cells comprising a host cell expressing a chimeric antigen receptor (CAR) directed against CD19, wherein the CAR comprises an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 13.
2 . The population of cells of claim 1 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 10.
3 . The population of cells of claim 1 , wherein the host cell is a T-cell.
4 . The population of cells of claim 1 , wherein the host cell is an NK cell.
5 . The population of cells of claim 2 , wherein the host cell is a T-cell.
6 . The population of cells of claim 2 , wherein the host cell is an NK cell.
7 . A pharmaceutical composition comprising the population of cells of claim 1 and a pharmaceutically acceptable carrier.
8 . A pharmaceutical composition comprising the population of cells of claim 2 and a pharmaceutically acceptable carrier.
9 . A pharmaceutical composition comprising the population of cells of claim 3 and a pharmaceutically acceptable carrier.
10 . A pharmaceutical composition comprising the population of cells of claim 4 and a pharmaceutically acceptable carrier.
11 . A pharmaceutical composition comprising the population of cells of claim 5 and a pharmaceutically acceptable carrier.
12 . A pharmaceutical composition comprising the population of cells of claim 6 and a pharmaceutically acceptable carrier.
13 . A population of cells comprising a host cell expressing a chimeric antigen receptor (CAR) comprising the amino acid sequence of each of the following that are present in SEQ ID NO: 4 or SEQ ID NO: 9:
(i) the extracellular spacer,
(ii) the transmembrane domain derived from a human CD8α molecule, and
(iii) the intracellular T-cell signaling domains derived from
(a) one or both of a human CD28 molecule and a human CD27 molecule, and
(b) a human CD3ζ molecule.
14 . The population of cells of claim 13 , wherein the host cell is a T-cell or an NK cell.
15 . A pharmaceutical composition comprising the population of cells of claim 14 and a pharmaceutically acceptable carrier.
16 . A population of cells comprising a host cell expressing a chimeric antigen receptor (CAR) comprising the amino acid sequence of each of the following that are present in SEQ ID NO: 10 or SEQ ID NO: 11:
(i) the extracellular spacer,
(ii) the transmembrane domain derived from a human CD8α molecule, and
(iii) the intracellular T-cell signaling domains derived from
(a) one or both of a human CD28 molecule and a human CD27 molecule, and
(b) the gamma chain of FcεRI.
17 . The population of cells of claim 16 , wherein the host cell is a T-cell or an NK cell.
18 . A pharmaceutical composition comprising the population of cells of claim 17 and a pharmaceutically acceptable carrier.
19 . A population of cells comprising a host cell expressing a chimeric antigen receptor (CAR) comprising the amino acid sequence of each of the following that are present in SEQ ID NO: 12 or SEQ ID NO: 13:
(i) the extracellular spacer,
(ii) the transmembrane domain derived from a human CD8α molecule, and
(iii) the intracellular T-cell signaling domains derived from a human CD28 molecule and the gamma chain of FcεRI.
20 . The population of cells of claim 19 , wherein the host cell is a T-cell or an NK cell.
21 . A pharmaceutical composition comprising the population of cells of claim 20 and a pharmaceutically acceptable carrier.