# US 2020/0399597 A1 · T-cell receptor-deficient t cell compositions

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- Number: US 2020/0399597 A1
- Document ID: US20200399597A1
- Status: Published application
- Kind: A1
- Application number: 15/930,571
- Filed: 2020-05-13
- Published: 2020-12-24
- Earliest claimed: 2009-10-29
- Assignees: Trustees of Dartmouth College
- Applicants: The Trustees of Dartmouth College
- Inventors: Charles L. SENTMAN
- Web page: https://patentgrep.com/patent/US20200399597A1

## CPC

- C12N 5/0636: {T lymphocytes}
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 39/0011: {Cancer antigens}
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/32: T-cell receptors [TCR]
- A61K 40/4224: {Molecules with a "CD" designation not provided for elsewhere}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61K 2039/5156: {expressing foreign proteins}
- A61K 2039/585: {wherein the target is cancer}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- A61K 2239/59: Reproductive system, e.g. uterus, ovaries, cervix or testes
- C12N 2501/515: CD3, T-cell receptor complex
- C12N 2510/02: Cells for production
- C12N 2511/00: Cells for large scale production
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

## Claims

### Claim 1

An isolated TCR-deficient T cell.

### Claim 2 (depends on 1)

The isolated TCR-deficient T cell of claim 1, wherein said T cell lacks cell-surface expression of at least one component of the T cell receptor complex.

### Claim 3 (depends on 1)

The isolated TCR-deficient T cell of claim 1, wherein said T cell lacks cell surface expression of all components of the T cell receptor complex.

### Claim 4

An isolated TCR-deficient T cell, wherein said T cell expresses at least one functional non-TCR receptor and does not express a functional TCR.

### Claim 5 (depends on 1, 2, 3)

An isolated T cell of any one of claims 1-3, wherein said T cell expresses at least one functional non-TCR receptor.

### Claim 6 (depends on 4, 5)

The isolated T cell of claims 4 or 5, wherein the at least one functional non-TCR receptor is a chimeric receptor comprising a ligand binding domain attached to a signaling domain.

### Claim 7 (depends on 6)

The isolated T cell of claim 6, wherein the ligand binding domain is obtained from NKG2D, NKG2A, NKG2C, NKG2F, LLT1, AICL, CD26, NKRP1, NKp30, NKp44, NKp46, CD244 (2B4), DNAM-1, or NKp80.

### Claim 8 (depends on 6)

The isolated T cell of claim 6, wherein the ligand binding domain is obtained from an anti-tumor chimeric antigen receptor or anti-tumor antibody.

### Claim 9 (depends on 8)

The isolated T cell of claim 8, wherein the anti-tumor antibody is obtained from an anti-Her2neu antibody or an anti-EGFR antibody.

### Claim 10 (depends on 6)

The isolated T cell of claim 6, wherein the signaling domain is obtained from CD3zeta, Dap10, CD28, 41BB, or CD40L.

### Claim 11 (depends on 4, 5)

The isolated T cell of claims 4 or 5, wherein the at least one functional non-TCR receptor binds MIC-A, MIC-B, Her2neu, EGFR, mesothelin, CD38, CD20, CD19, PSA, MUC1, MUC2, MUC3A, MUC3B, MUC4, MUC5AC, MUC5B, MUC6, MUC7, MUC8, MUC12, MUC13, MUC15, MUC16, MUC17, MUC19, MUC20, estrogen receptor, progesterone receptor, RON, or one or more members of the ULBP/RAET1 family.

### Claim 12 (depends on 11)

The isolated T cell of claim 11, wherein the one or more members of the ULBP/RAET1 family include ULBP1, ULBP2, ULBP3, ULBP4, ULBP5, and ULBP6.

### Claim 13 (depends on 4, 5)

The isolated T cell of claims 4 or 5, wherein the at least one functional non-TCR receptor binds to virus antigen or viral-induced antigen found on the surface of an infected cell.

### Claim 14 (depends on 13)

The isolated T cell of claim 13, wherein the virus is selected from HCMV, HIV, EBV, HBV, HCV, Ebola virus, a hantavirus, or VSV.

### Claim 15 (depends on 1)

The isolated T cell of claim 1 which is human.

### Claim 16 (depends on 1)

The isolated T cell of claim 1 which comprises a gene that encodes a dominant selectable marker.

### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A composition comprising an isolated T cell of any one of claims 1-16.

### Claim 18 (depends on 17)

The composition of claim 17, comprising a therapeutically-effective amount of said isolated TCR-deficient T cells.

### Claim 19 (depends on 17)

The composition of claim 17, comprising a pharmaceutical carrier.

### Claim 20 (depends on 18)

A method of preventing or treating cancer in an individual in need thereof, comprising administering the composition of claim 18 to said individual.

### Claim 21 (depends on 18)

A method of preventing or treating graft versus host disease in an individual having transplant surgery, comprising administering the composition of claim 18 to said individual prior to the transplant surgery.

### Claim 22 (depends on 18)

A method of treating infection in an individual in need thereof, comprising administering the composition of claim 18 to said individual.

### Claim 23 (depends on 18)

A method of treating one or more autoimmune disorders in an individual in need thereof, comprising administering the composition of claim 18 to said individual.

### Claim 24 (depends on 18)

A method of preventing or treating transplantation rejection in an individual having transplant surgery, comprising administering the composition of claim 18 to said individual prior to the transplant surgery.

### Claim 25 (depends on 18)

A method of treating radiation sickness in an individual in need thereof, comprising administering the composition of claim 18 to said individual.

### Claim 26 (depends on 4, 5)

A method of preventing or treating cancer in an individual in need thereof, comprising administering a therapeutically-effective amount of the isolated T cells of claim 4 or 5 to said individual.

### Claim 27 (depends on 4, 5)

A method of preventing or treating graft versus host disease in an individual having transplant surgery, comprising administering a therapeutically-effective amount of the isolated T cells of claim 4 or 5 to said individual prior to the transplant surgery.

### Claim 28 (depends on 4, 5)

A method of treating infection in an individual in need thereof, comprising administering a therapeutically-effective amount of the isolated T cells of claim 4 or 5 to said individual.

### Claim 29 (depends on 4, 5)

A method of treating one or more autoimmune disorders in an individual in need thereof, comprising administering a therapeutically-effective amount of the isolated T cells of claim 4 or 5 to said individual.

### Claim 30 (depends on 4, 5)

A method of preventing or treating transplantation rejection in an individual having transplant surgery, comprising administering a therapeutically-effective amount of the isolated T cells of claim 4 or 5 to said individual prior to the transplant surgery.

### Claim 31 (depends on 4, 5)

A method of treating radiation sickness in an individual in need thereof, comprising administering a therapeutically-effective amount of the isolated T cells of claim 4 or 5 to said individual.

### Claim 32

A T cell bank comprising TCR-deficient T cells of different tissue HLA types, wherein said T cell bank comprises different T cell containing compositions each composition containing T cells of a specific HLA type, which are TCR-deficient.

### Claim 33 (depends on 32)

The T cell bank of claim 32 which comprises T cells of at least 10 different HLA tissue types.

### Claim 34 (depends on 32)

The T cell bank of claim 32 which comprises T cells of from about 50-100 different HLA tissue types.

### Claim 35 (depends on 32)

The T cell bank of claim 32 which contains T cells that are engineered to stably lack cell-surface expression of at least one component of the T cell receptor complex.