Chimeric antigen receptors targeted to PSCA
Chimeric transmembrane immunoreceptors (CAR) targeted to PSCA are described.
1 . A nucleic acid molecule encoding a chimeric antigen receptor (CAR) selected from the group consisting of:
(a) a CAR comprising a Prostate Stem Cell Antigen (PSCA) scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 9, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21;
(b) a CAR comprising a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 2, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21; or
(c) a CAR comprising a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 10, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
2 . The nucleic acid molecule of claim 1 , wherein the CAR comprises: PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 9, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
3 . The nucleic acid molecule of claim 1 , wherein the CAR comprises: a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 2, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
4 . The nucleic acid molecule of claim 1 , wherein the CAR comprises: a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 10, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
5 . A population of human T cells comprising a nucleic acid encoding a CAR selected from the group consisting of:
(a) a CAR comprising a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 9, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21;
(b) a CAR comprising a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 2, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21; or
(c) a CAR comprising a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 10, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
6 . The population of human T cells of claim 5 , wherein the CAR comprises: PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 9, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
7 . The population of human T cells of claim 5 , wherein the CAR comprises: a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 2, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
8 . The population of human T cells of claim 5 , wherein the CAR comprises: a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 10, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
9 . The population of human T cells of claim 5 , wherein the population of T cells comprises central memory T cells.
10 . A CAR selected from the group consisting of:
(a) a CAR comprising a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 9, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21;
(b) a CAR comprising a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 2, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21; or
(c) a CAR comprising a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 10 a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
11 . The CAR of claim 10 , wherein the CAR comprises: PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 9, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
12 . The CAR of claim 10 , wherein the CAR comprises: a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 2, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
13 . The CAR of claim 10 , wherein the CAR comprises: a PSCA scFV comprising the amino acid sequence of SEQ ID NO: 38, a spacer comprising the amino acid sequence of SEQ ID NO: 10, a CD4 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 16, a 41-BB co-stimulatory domain comprising the amino acid sequence of SEQ ID NO: 24, and CD3ζ domain comprising the amino acid sequence of SEQ ID NO: 21.
14 . A method for treating a human patient having a cancer expressing PSCA, the method comprising administering to the patient the population of human T cells of claim 5 .
15 . The method of claim 14 , wherein the population of human T cells are allogeneic to the patient.
16 . The method of claim 15 , wherein the cancer is prostate cancer.
17 . The method of claim 15 , wherein the cancer is a bone metastasis of prostate cancer.
18 . The method of claim 15 , wherein the cancer is pancreatic cancer.
19 . The method of claim 15 , wherein the CAR comprises an amino acid sequence selected from SEQ ID NOs: 26, 28, 30, 32, 34, and 36.