# US 12,215,154 B2 · Compositions and methods for targeting γδ T cells with chimeric antigen receptors

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- Number: US 12,215,154 B2
- Document ID: US12215154B2
- Status: Granted
- Kind: B2
- Application number: 16/963,047
- Filed: 2019-01-18
- Published: 2020-10-29
- Granted: 2025-02-04
- Earliest claimed: 2018-01-19
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: Aimee S. Payne; Christoph T. Ellebrecht
- Web page: https://patentgrep.com/patent/US12215154B2

## CPC

- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/32: T-cell receptors [TCR]
- A61K 40/4211: {CD19 or B4}
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61P 35/00: Antineoplastic agents
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70517: {CD8}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- A61K 2239/28: Expressing multiple CARs, TCRs or antigens
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2319/02: containing a signal sequence
- 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

The invention includes compositions comprising a chimeric antigen receptor (CAR) specific for an GD T Cell receptor (anti-GD TCR CAR), vectors comprising the same, compositions comprising anti-GD TCR CAR vectors packaged in viral particles, and recombinant T cells or other effector cells comprising the anti-GD TCR CAR of the invention. The invention also includes methods of making a genetically modified T cell expressing an anti-GD TCR CAR wherein the expressed CAR comprises an extracellular domain that binds to GD T cells or to cells expressing a GD TCR.

## Claims

### Claim 1

An isolated nucleic acid comprising a nucleic acid sequence encoding an anti-GD TCR CAR comprising the amino acid sequence of SEQ ID NO: 1.

### Claim 2 (depends on 1)

The isolated nucleic acid of claim 1, wherein the nucleic acid sequence encoding the anti-GD TCR CAR comprises SEQ ID NO: 9.

### Claim 3 (depends on 1)

The isolated nucleic acid of claim 1, wherein the light chain is encoded by the nucleic acid sequence of SEQ ID NO: 11 or the heavy chain is encoded by the nucleic acid sequence of SEQ ID NO: 13.

### Claim 4 (depends on 1)

The isolated nucleic acid of claim 1, wherein the VH3-23 signal peptide is encoded by the nucleic acid sequence of SEQ ID NO: 10.

### Claim 5 (depends on 1)

The isolated nucleic acid of claim 1, wherein the CD8 alpha chain hinge and transmembrane domain are encoded by a nucleic acid sequence comprising the sequence of SEQ ID NO: 14.

### Claim 6 (depends on 1)

The isolated nucleic acid of claim 1, wherein the nucleic acid sequence encoding the peptide linker comprises SEQ ID NO: 12.

### Claim 7 (depends on 1)

The isolated nucleic acid of claim 1, wherein the nucleic acid sequence encoding the CD137 intracellular domain comprises SEQ ID NO: 15.

### Claim 8 (depends on 1)

The isolated nucleic acid of claim 1, wherein the nucleic acid sequence encoding the CD3 zeta signaling domain comprises SEQ ID NO: 16.

### Claim 9 (depends on 1)

A vector comprising the isolated nucleic acid of claim 1.

### Claim 10 (depends on 9)

The vector of claim 9, wherein the vector is a lentiviral vector.

### Claim 11 (depends on 10)

The vector of claim 10, wherein the vector is a RNA vector.

### Claim 12 (depends on 1)

An isolated anti-GD TCR CAR encoded by the nucleic acid of claim 1.

### Claim 13 (depends on 1)

A genetically modified cell comprising the isolated nucleic acid of claim 1.

### Claim 14 (depends on 13)

The cell of claim 13, wherein the cell expresses the anti-GD TCR CAR and has high affinity for GD T cells.

### Claim 15 (depends on 13)

The cell of claim 13, wherein the cell expresses the anti-GD TCR CAR and induces killing of GD T cells or cells expressing GD TCR.

### Claim 16 (depends on 13)

The cell of claim 13, wherein the cell is selected from the group consisting of a helper T cell, a cytotoxic T cell, a memory T cell, regulatory T cell, a natural killer cell, a cytokine induced killer cell, a cell line thereof, a T memory stem cell and other effector cell.

### Claim 17 (depends on 13)

The cell of claim 13, wherein an endogenous CD3 and an endogenous MHCI of the cell has been knocked out using a CRISPR/CAS system.

### Claim 18 (depends on 13)

A method for treating a GD T cell related disease in a subject, the method comprising: administering to the subject an effective amount of the genetically modified T cell of claim 13.

### Claim 19 (depends on 18)

The method of claim 18, wherein the GD T cell related disease is an inflammatory or autoimmune selected from the group consisting of juvenile idiopathic arthritis, Behcet's disease, alopecia areata, systemic sclerosis, atherosclerosis, psoriasis, myositis, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type I diabetes, ankylosing spondylitis, autoimmune uveitis, Sjogren's syndrome, systemic lupus, and chronic cutaneous lupus.

### Claim 20 (depends on 18)

The method of claim 18, wherein the GD T cell related disease is a GD T cell lymphoma (GDTCL).

### Claim 21 (depends on 18)

The method of claim 18, wherein the subject is a human.

### Claim 22 (depends on 18)

The method of claim 18, wherein the modified T cell targets a GD T cell or a cell expressing GD TCR.