# US 2024/0197779 A1 · Anti-cd83 chimeric antigen receptor expressing t regulatory cells

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- Number: US 2024/0197779 A1
- Document ID: US20240197779A1
- Status: Published application
- Kind: A1
- Application number: 18/478,247
- Filed: 2023-09-29
- Published: 2024-06-20
- Earliest claimed: 2018-02-23
- Assignees: H. Lee Moffitt Cancer Center and Research Institute, Inc.
- Applicants: H. Lee Moffitt Cancer Center and Research Institute, Inc.
- Inventors: Marco Davila; Brian Betts
- Web page: https://patentgrep.com/patent/US20240197779A1

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 40/10: characterised by the cell type used
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/22: Immunosuppressive or immunotolerising
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/418: {Antigens related to induction of tolerance to non-self}
- A61K 40/421: {Immunoglobulin superfamily}
- A61K 40/4211: {CD19 or B4}
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- A61K 2039/505: {comprising antibodies}
- A61K 2239/38: characterised by the dose, timing or administration schedule
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) in subjects receiving donor cells. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to suppress alloreactive donor cells. Therefore, also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the disclosed regulatory T cells engineered to express the disclosed CARs. Also disclosed is a method of preventing rejection of off-the-shelf therapeutic immune effector cells, such as CAR-T cells, in a subject that involves administering to the subject an effective amount of a regulatory T cell genetically modified with a disclosed CD83-specific CAR.

## Claims

### Claim 1

A method of suppressing alloreactive donor cells in a subject receiving transplant donor cells, the method comprising administering to the subject an effective amount of a first immune effector cell genetically modified to express a first chimeric antigen receptor (CAR) polypeptide, comprising a CD83 antigen binding domain, a transmembrane domain, an intracellular signaling domain, and a co-stimulatory signaling region, thereby suppressing alloreactive donor cells in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the first immune effector cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a B cell, an innate lymphoid cell (ILC), a cytokine induced killer (CIK) cell, a cytotoxic T lymphocyte (CTL), a lymphokine activated killer (LAK) cell, and a regulatory T (Treg) cell.

### Claim 3 (depends on 1)

The method of claim 1, wherein the donor cells are bone marrow cells comprising alloreactive T-cells, dendritic cells, or a combination thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the transplant donor cells comprise a second immune effector cell genetically modified to express a second CAR polypeptide.

### Claim 5 (depends on 4)

The method of claim 4, wherein the second immune effector cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a B cell, an innate lymphoid cell (ILC), a cytokine induced killer (CIK) cell, a cytotoxic T lymphocyte (CTL), a lymphokine activated killer (LAK) cell, and a regulatory T (Treg) cell.

### Claim 6 (depends on 4)

The method of claim 4, wherein the first CAR polypeptide comprises in an ectodomain a targeting agent that binds an antigen selected from the group consisting of CD19, CD22, CD123, CD38, CLL-1, TEM8/ANTXR1, CD56, NKG2D, B7H6, CD4, Gp120, Erb-B, SLAMF7, CD7, EGFR, TAG-72, MMG49, Integrin β7, FLT3, MESO, CD70, FOLR1, CD33, CD171, CD20, GD2, HER2, EGFRvIII, CSPG4, DNAX, BCMA, LeY, CD30, GPC3, CS1, CD138, Nectin4/FAP, CEA, EpCAM, PSCA, MUC1, CD80, CD86, CTLA-4, PD-1, CD10, EGFR806, IL 12, TLR-9, CD83, CLEC12A, CD99, IL13Rα2, SSTR2, and GPC3.

### Claim 7 (depends on 1)

The method of claim 1, wherein the transplant donor cells are not HLA matched to the subject.

### Claim 8 (depends on 7)

The method of claim 7, wherein the transplant donor cells have less than 3, 4, 5, or 6 HLA-matched markers as the subject.

### Claim 9 (depends on 1)

The method of claim 1, wherein the subject has not received an immunosuppressant.

### Claim 10 (depends on 1)

The method of claim 1, wherein the CD83 antigen binding domain is a single-chain variable fragment (scFv) of an antibody that specifically binds CD83.

### Claim 11 (depends on 9)

The method of claim 9, wherein the anti-CD83 scFv comprises a variable heavy (VH) domain having CDR1, CDR2 and CDR3 sequences and a variable light (VL) domain having CDR1, CDR2 and CDR3 sequences, wherein the CDR1 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:1, SEQ ID NO:7, or SEQ ID NO:13; the CDR2 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:2, SEQ ID NO:8, or SEQ ID NO:14; the CDR3 sequence of the VH domain comprises the amino acid sequence SEQ ID NO:3, SEQ ID NO:9, or SEQ ID NO:15; the CDR1 sequence of the VL comprises the amino acid sequence SEQ ID NO:4, SEQ ID NO:10, or SEQ ID NO:16; the CDR2 sequence of the VL domain comprises the amino acid sequence SEQ ID NO:5, SEQ ID NO:11, or SEQ ID NO:17; and the CDR3 sequence of the VL domain comprises the amino acid sequence SEQ ID NO:6, SEQ ID NO:12, or SEQ ID NO:18.

### Claim 12 (depends on 10)

The method of claim 10, wherein the anti-CD83 scFv VH domain comprises the amino acid sequence SEQ ID NO:19, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, or SEQ ID NO:53, and wherein the anti-CD83 scFv VL domain comprises the amino acid sequence SEQ ID NO:20, SEQ ID NO:54, or SEQ ID NO:55.

### Claim 13 (depends on 11)

The method of claim 11, wherein the anti-CD83 scFv comprises the amino acid sequence SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, or SEQ ID NO:71.

### Claim 14 (depends on 1)

The method of claim 1, wherein the costimulatory signaling region comprises the cytoplasmic domain of a costimulatory molecule selected from the group consisting of CD27, CD28, 4-1 BB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, and any combination thereof.

### Claim 15 (depends on 1)

The method of claim 1, further comprising administering to the subject a checkpoint inhibitor.

### Claim 16 (depends on 14)

The method of claim 14, wherein the checkpoint inhibitor comprises an anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, or a combination thereof.

### Claim 17

A method for treating a subject, comprising co-administering to the subject a therapeutic amount of a first non-autologous, non-HLA-matched immune effector cell genetically modified to express a first chimeric antigen receptor (CAR) polypeptide and a second non-autologous, non-HLA-matched immune effector cell genetically modified to express a second CAR polypeptide comprising a CD83 antigen binding domain.

### Claim 18 (depends on 17)

The method of claim 17, wherein the second immune effector cell is selected from the group consisting of a T cell, a Natural Killer (NK) cell, a B cell, an innate lymphoid cell (ILC), a cytokine induced killer (CIK) cell, a cytotoxic T lymphocyte (CTL), a lymphokine activated killer (LAK) cell, and a regulatory T (Treg) cell.

### Claim 19 (depends on 17)

The method of claim 17, wherein the first CAR polypeptide comprises in an ectodomain a targeting agent that binds an antigen selected from the group consisting of CD19, CD22, CD123, CD38, CLL-1, TEM8/ANTXR1, CD56, NKG2D, B7H6, CD4, Gp120, Erb-B, SLAMF7, CD7, EGFR, TAG-72, MMG49, Integrin β7, FLT3, MESO, CD70, FOLR1, CD33, CD171, CD20, GD2, HER2, EGFRvIII, CSPG4, DNAX, BCMA, LeY, CD30, GPC3, CS1, CD138, Nectin4/FAP, CEA, EpCAM, PSCA, MUC1, CD80, CD86, CTLA-4, PD-1, CD10, EGFR806, IL 12, TLR-9, CD83, CLEC12A, CD99, IL13Rα2, SSTR2, and GPC3.

### Claim 20 (depends on 17)

The method of claim 17, wherein the subject has not received an immunosuppressant.