Anti-dinitrophenol chimeric antigen receptors

Patent metadata

Field	Value
Publication number	US-12570716-B2
Application number	US-202117758959-A
Country	US
Kind code	B2
Filing date	Feb 2, 2021
Priority date	Feb 4, 2020
Publication date	Mar 10, 2026
Grant date	Mar 10, 2026

Abstract

Embodiments provided herein include methods and compositions comprising anti-dinitrophenol chimeric antigen receptors (CARs). Some embodiments include nucleic acids encoding such CARs, polypeptides encoded by such nucleic acids, cells comprising such nucleic acids or polypeptides, and methods utilizing such cells. Some embodiments also include the use of dinitrophenol (DNP) and derivatives thereof.

First claim

What is claimed is:

1 . A chimeric antigen receptor (CAR) comprising:
a ligand binding domain which specifically binds to a dinitrophenol (DNP) moiety, wherein the ligand binding domain comprises (i) an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO:1, SEQ ID NO:7 or SEQ ID NO:12; or (ii) an amino acid sequence having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:11; a spacer; a transmembrane domain; and an intracellular signaling domain.

2 . A system comprising:
(a) an effector cell comprising the CAR of claim 1 ; and (b) a composition comprising a dinitrophenol (DNP) moiety, wherein the CAR specifically binds to the DNP moiety.

3 . The system of claim 2 , wherein the DNP moiety is attached to the target cell via an antibody or antigen binding fragment thereof that binds to the target cell; or via a lipid integrated into the target cell's surface.

4 . The system of claim 3 , wherein the target cell is a cancer cell.

5 . The system of claim 4 , wherein the cancer cell is selected from the group consisting of a breast cancer cell, brain cancer cell, colon cancer cell, renal cancer cell, pancreatic cancer cell, and ovarian cancer cell.

6 . The CAR of claim 1 , wherein the ligand binding domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in any of SEQ ID NO:1, SEQ ID NO:9 and SEQ ID NO:10.

7 . The CAR of claim 1 , wherein the ligand binding domain comprises an amino acid sequence having at least 96% sequence identity to SEQ ID NO:1.

8 . The CAR of claim 1 , wherein the spacer comprises an IgG4 hinge domain, an IgG4 hinge-CH3 domain, or an IgG4 hinge-CH2-CH3 domain.

9 . The CAR of claim 1 , wherein the spacer has a length of at least 229 consecutive amino acid residues.

10 . The CAR of claim 1 , wherein the spacer comprises the amino acid sequence set forth in SEQ ID NO:20.

11 . The CAR of claim 1 , wherein the transmembrane domain comprises a CD28 transmembrane domain, and the intracellular signaling domain comprises a portion of CD3 zeta and/or a portion of 4-1BB.

12 . The system of claim 2 , wherein the ligand binding domain comprises an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in any of SEQ ID NO:1, SEQ ID NO:9 and SEQ ID NO:10.

13 . The system of claim 2 , wherein the ligand binding domain comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO:1 or SEQ ID NO:2.

14 . The system of claim 2 , wherein the spacer comprises an IgG4 hinge domain, an IgG4 hinge-CH3 domain, or an IgG4 hinge -CH2-CH3 domain.

15 . The system of claim 2 , wherein the spacer has a length of at least 229 consecutive amino acid residues.

16 . The system of claim 2 , wherein the spacer comprises the amino acid sequence set forth in SEQ ID NO:20.

17 . The system of claim 2 , wherein the transmembrane domain comprises a CD28 transmembrane domain, and the intracellular signaling domain comprises a portion of CD3 zeta and/or a portion of 4-1BB.

18 . The system of claim 2 , wherein the DNP moiety is joined to a phospholipid.

19 . The system of claim 18 , wherein the phospholipid is a phospholipid ether (PLE).

20 . The system of claim 19 , wherein the DNP moiety is joined to the PLE by a PEG spacer, and the DNP moiety joined to the PLE by the PEG spacer comprises a structure:

Assignees

• Seattle Childrens Hospital

Inventors

• Jensen Michael C
• Matthaei James F
• Cheng Joseph K

Classifications

• A61K40/414

  Nervous system antigens · CPC title

• A61K40/31

  Chimeric antigen receptors [CAR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• A61K2239/49

  Breast · CPC title

• A61K2239/31

  characterized by the route of administration · CPC title