IP Library › Granted Patent US 12686707

Granted Patent B2

US 12686707 · App. 18/046,728 · Granted Jul 21, 2026

Anti-STEAP2 chimeric antigen receptors and uses thereof

Inventors: Emily Bosco (Wilmington, DE); Dewald Van Dyk (Wilmington, DE); Gordon Moody (Wilmington, DE); Christine Fazenbaker (Gaithersburg, MD); Chien-Ying Chang (Gaithersburg, MD)

Assignee: MEDIMMUNE, LLC

C07K14/705 A61P35/04 C12N15/86 C07K2319/03 C07K2319/30

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Quick Facts

Patent No.: US 12686707
App. No.: 18/046,728
Granted: Jul 21, 2026
Kind: B2

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Abstract

The disclosure provides chimeric antigen receptors and antibodies that comprise antigen-binding domains that specifically bind human STEAP2, nucleotides that encode the same, cells comprising the same, and methods of using the same in the treatment of cancer (e.g., prostate cancer).

Claims (107)

1 . A polynucleotide comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR), the CAR comprising

(i) an antigen-binding domain that binds an epitope on human six transmembrane epithelial antigen of prostate-2 (STEAP2);

(ii) a transmembrane domain; and

(iii) an intracellular domain,

wherein the antigen-binding domain comprises:

(a) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 2, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 3, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 5, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 6;

(b) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 11, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 12, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 13, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 14, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 15, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16;

(c) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 21, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 22, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 23, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 25, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26;

(d) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 31, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 32, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 33, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 34, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 35, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36;

(e) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 42, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 43, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 45, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 46; or

(f) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 91, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 92, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 93, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 94, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 95, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 96.

2 . The polynucleotide of claim 1 , wherein the antigen-binding domain comprises:

(a) a VH comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 7, and a VL comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 8;

(b) a VH comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and a VL comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18;

(c) a VH comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 27, and a VL comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 28;

(d) a VH comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 37, and a VL comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 38;

(e) a VH comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 47, and a VL comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48; or

(f) a VH comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 97, and a VL comprising an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 98.

3 . The polynucleotide of claim 1 , wherein the antigen-binding domain comprises:

(a) a VH comprising the amino acid sequence set forth in SEQ ID NO: 7, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 8;

(b) a VH comprising the amino acid sequence set forth in SEQ ID NO: 17, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 18;

(c) a VH comprising the amino acid sequence set forth in SEQ ID NO: 27, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 28;

(d) a VH comprising the amino acid sequence set forth in SEQ ID NO: 37, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 38;

(e) a VH comprising the amino acid sequence set forth in SEQ ID NO: 47, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 48;

(f) a VH comprising the amino acid sequence set forth in SEQ ID NO: 57, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 58;

(g) a VH comprising the amino acid sequence set forth in SEQ ID NO: 67, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 68;

(h) a VH comprising the amino acid sequence set forth in SEQ ID NO: 77, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 78;

(i) a VH comprising the amino acid sequence set forth in SEQ ID NO: 87, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 88; or

(j) a VH comprising the amino acid sequence set forth in SEQ ID NO: 97, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 98.

4 . The polynucleotide of claim 1 , wherein the intracellular domain comprises a costimulatory domain selected from the group consisting of the intracellular domain of CD3z, a CD28 co-stimulatory domain, a CD27 co-stimulatory domain, a 4-1BB co-stimulatory domain, an ICOS co-stimulatory domain, an OX-40 co-stimulatory domain, a GITR co-stimulatory domain, a CD2 co-stimulatory domain, an IL-2Rβ co-stimulatory domain, an MyD88/CD40a CD28 co-stimulatory domain, and any combination thereof.

5 . The polynucleotide of claim 1 , wherein the CAR comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10.

6 . The polynucleotide of claim 1 , which further encodes an armoring molecule, wherein the armoring molecule counters immunosuppression of a cell in a tumor microenvironment when expressed on a surface of the cell.

7 . The polynucleotide of claim 6 , wherein the armoring molecule comprises a dominant-negative TGF-β receptor type 2 (TGFβRIIDN), and wherein the armoring molecule comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 105.

8 . A vector or a set of vectors comprising the polynucleotide of claim 7 .

9 . A cell comprising the polynucleotide of claim 7 .

10 . A cell comprising (i) a polynucleotide encoding a chimeric antigen receptor (CAR) that binds human STEAP2 and (ii) a polynucleotide encoding an armoring molecule, wherein the CAR comprises an antigen-binding domain comprising a VH and a VL, wherein the VH comprises a VH-CDR1, a VH-CDR2, a VH-CDR3, and wherein the VL comprises a VL-CDR1, a VL-CDR2, and VL-CDR3; and wherein

(a) the VL-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 1, the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 2, the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 3, the VH-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 4, the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 5, and the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 6;

(b) the VL-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 11, the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 12, the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 13, the VH-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 14, the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 15, and the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 16;

(c) the VL-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 21, the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 22, the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 23, the VH-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 24, the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 25, and the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 26;

(d) the VL-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 31, the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 32, the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 33, the VH-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 34, the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 35, and the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 36;

(e) the VL-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 41, the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 42, the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 43, the VH-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 44, the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 45, and the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 46; or

(f) the VL-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 91, the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 92, the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 93, the VH-CDR1 comprises the amino acid sequence set forth in SEQ ID NO: 94, the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 95, and the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 96.

11 . The cell of claim 10 , wherein

(a) the VH comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 7, and the VL comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 8;

(b) the VH comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and the VL comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18;

(c) the VH comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 27, and the VL comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 28;

(d) the VH comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 37, and the VL comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 38;

(e) the VH comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 47, and the VL comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 48;

(f) the VH comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 57, and the VL comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 58;

(g) the VH comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 67, and the VL comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 68;

(h) the VH comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 77, and the VL comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 78;

(i) the VH comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 87, and the VL comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 88; or

(j) the VH comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 97, and the VL comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 98.

12 . The cell of claim 10 , wherein the CAR comprises an antigen-binding domain that comprises the amino acid sequence of SEQ ID NO: 9.

13 . The cell of claim 12 , wherein the armoring molecule comprises a dominant-negative TGF-β receptor type 2 (TGFβRIIDN), and wherein, the armoring molecule comprises an amino acid sequence having at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or 100% sequence identity to the amino acid sequence set forth in SEQ ID NO: 105.

14 . A cell comprising a chimeric antigen receptor (CAR) that binds human STEAP2, wherein the CAR comprises an antigen-binding domain that comprises:

a) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 2, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 3, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 5, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 6;

b) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 11, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 12, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 13, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 14, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 15, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 16;

c) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 21, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 22, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 23, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 24, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 25, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 26;

d) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 31, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 32, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 33, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 34, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 35, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 36; or

e) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 41, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 42, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 43, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 44, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 45, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 46; or

f) a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 91, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 92, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 93, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 94, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 95, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 96.

15 . An antibody or an antigen-binding portion thereof that specifically binds human STEAP2, comprising a variable heavy chain region (VH) and a variable light chain region (VL), wherein the VH comprises a VH complementarity determining region 1 (VH-CDR1), a VH-CDR2, a VH-CDR3; and wherein the VL comprises a VL-CDR1, a VL-CDR2, and VL-CDR3, wherein:

16 . The antibody or an antigen-binding portion thereof of claim 15 , wherein:

17 . A pharmaceutical composition comprising the cell of claim 13 and a pharmaceutically acceptable excipient.

18 . A method of treating a cancer in a subject in need thereof, comprising administering to the subject the cell of claim 13 .

19 . A polynucleotide comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR), the CAR comprising:

(i) an antigen-binding domain that binds an epitope on human six transmembrane epithelial antigen of prostate-2 (STEAP2) comprising a VL-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 1, a VL-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 2, a VL-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 3, a VH-CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, a VH-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 5, a VH-CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 6;

(ii) a transmembrane domain; and

(iii) an intracellular domain.

20 . The polynucleotide of claim 19 , wherein the antigen-binding domain comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 7, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 8.

21 . The polynucleotide of claim 19 , wherein the CAR comprises the amino acid sequence as set forth in SEQ ID NO: 10.

22 . The polynucleotide of claim 19 , wherein the CAR comprises the amino acid sequence set forth in SEQ ID NO: 106.

23 . The polynucleotide of claim 19 , comprising nucleotide sequence set forth in SEQ ID NO: 107.

24 . The cell of claim 12 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 10.

25 . The cell of claim 12 , wherein the armoring molecule comprises an amino acid sequence of SEQ ID NO: 105.

26 . The cell of claim 14 , wherein the antigen-binding domain comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 7, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 8.

27 . The cell of claim 26 , wherein the antigen-binding domain that comprises the amino acid sequence of SEQ ID NO: 9.

28 . The cell of claim 27 , wherein the CRA comprises the amino acid sequence of SEQ ID NO: 10.

29 . The cell of claim 27 , wherein the CAR comprises the amino acid sequence of SEQ ID NO: 106.

30 . The cell of claim 14 , comprising the nucleotide sequence set forth in SEQ ID NO: 107.

31 . A method of treating a cancer in a subject in need thereof, comprising administering to the subject the cell of claim 25 .

32 . A method of treating a cancer in a subject in need thereof, comprising administering to the subject the cell of claim 28 .

33 . The polynucleotide of claim 1 , wherein the CAR comprises the amino acid sequence set forth in SEQ ID NO: 10.

34 . A pharmaceutical composition comprising the cell of claim 24 and a pharmaceutically acceptable excipient.

35 . A method of treating a cancer in a subject in need thereof, comprising administering to the subject the cell of claim 24 .

36 . A pharmaceutical composition comprising the cell of claim 29 and a pharmaceutically acceptable excipient.

37 . A method of treating a cancer in a subject in need thereof, comprising administering to the subject the cell of claim 29 .

38 . A vector comprising the polynucleotide of claim 23 .

39 . A cell comprising the vector of claim 38 .

40 . A chimeric antigen receptor (CAR) that binds human STEAP2 comprising the amino acid sequence of SEQ ID NO: 10 or SEQ ID NO: 106.