# US 10,765,728 B2 · Method for generating immune cells resistant to arginine and/or tryptophan depleted microenvironment

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- Number: US 10,765,728 B2
- Document ID: US10765728B2
- Status: Granted
- Kind: B2
- Application number: 15/302,913
- Filed: 2015-04-10
- Published: 2017-02-09
- Granted: 2020-09-08
- Earliest claimed: 2014-04-11
- Assignees: Cellectis
- Applicants: Cellectis
- Inventors: Laurent Poirot; Mathieu Simon
- Web page: https://patentgrep.com/patent/US10765728B2

## CPC

- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- 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 39/001102: {Receptors, cell surface antigens or cell surface determinants}
- A61K 39/001104: {Epidermal growth factor receptors [EGFR]}
- A61K 39/001112: {CD19 or B4}
- A61K 39/001129: {Molecules with a "CD" designation not provided for elsewhere}
- 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 40/42: Cancer antigens
- A61P 35/00: Antineoplastic agents
- A61P 37/02: Immunomodulators
- C07K 14/4703: {Inhibitors; Suppressors}
- C07K 14/4705: {stimulating, promoting or activating activity}
- C12N 9/12: transferring phosphorus containing groups, e.g. kinases (2.7)
- C12Y 207/11001: Non-specific serine/threonine protein kinase (2.7.11.1), i.e. casein kinase or checkpoint kinase
- A61K 2039/515: {Animal cells}
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES

## Abstract

The present invention pertains to engineered immune cells, method for their preparation and their use as medicament, particularly for immunotherapy. The engineered immune cells of the present invention are characterized in that at least one gene selected from a gene encoding GCN2 and a gene encoding PRDM1 is inactivated or repressed. Such modified Immune cells are resistant to an arginine and/or tryptophan depleted microenvironment caused by, e.g., tumor cells, which makes the immune cells of the invention particularly suitable for immunotherapy. The invention opens the way to standard and affordable adoptive immunotherapy strategies using immune cells for treating different types of malignancies.

## Claims

### Claim 1

A method of treating an arginase I producing cancer that inhibits T-cell activity, comprising administering to a patient in need thereof a therapeutically effective amount of an engineered human T-cell comprising at least one insertion, deletion, or addition to a GCN2 or PRDM1 gene conferring arginase resistance, wherein said cancer is selected from the group consisting of lung cancer, breast cancer, uterine cancer, prostate cancer, kidney cancer, colon cancer, liver cancer, pancreatic cancer, and skin cancer.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the GCN2 gene or PRDM1 gene is inactivated by cleavage with a rare-cutting endonuclease.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the T-cell is an autologous T-cell.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the T-cell is from a donor.