# US 2018/0021418 A1 · Engineered t cells and uses therefor

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- Number: US 2018/0021418 A1
- Document ID: US20180021418A1
- Status: Published application
- Kind: A1
- Application number: 15/542,915
- Filed: 2016-01-11
- Published: 2018-01-25
- Earliest claimed: 2015-01-12
- Assignees: Pieris Pharmaceuticals GmbH
- Applicants: Pieris Pharmaceuticals GmbH
- Inventors: Marlon Hinner
- Web page: https://patentgrep.com/patent/US20180021418A1

## CPC

- C07K 14/70521: {CD28, CD152}
- 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 40/36: Immune checkpoint inhibitors
- A61K 40/4209: {Hepatocyte growth factor receptor [HGFR] or c-met]}
- A61K 40/4215: {Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30}
- A61K 40/4242: {Transcription factors, e.g. SOX or c-MYC}
- A61K 40/4261: {Proteoglycans, e.g. glypican, brevican or CSPG4}
- C07K 14/47: from mammals
- C07K 14/5434: {IL-12}
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- C12N 5/0636: {T lymphocytes}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2318/20: Antigen-binding scaffold molecules wherein the scaffold is not an immunoglobulin variable region or antibody mimetics
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/22: containing a Strep-tag
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K 2319/74: containing a fusion for binding to a cell surface receptor
- C12N 2510/00: Genetically modified 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Lipocalin muteins specific to a predetermined antigen can be transduced into a T cell to bring therapeutic benefits to patients in need. In one example, a lipocalin mutein specific to a predetermined antigen (e.g., a target differentially expressed on the surface of a tumor cell) can be transduced into a T cell membrane to serve as an antigen receptor, offering benefits over conventionally deployed antibody-derived protein moieties such as a single chain variable fragment (scFv). Benefits include a more stable structure, leading to superior target engagement, for example. Further, lipocalin muteins specific to a predetermined antigen (e.g. an immunomodulatory target such as an immune checkpoint or costimulatory molecule) can be transduced into a T cell for secretion thereby, bringing an added therapeutic benefit. Specific examples of such modified T cells and methods of making and using the same are provided herein.

## Claims

### Claim 1

A T cell having a cellular membrane, where said T cell is modified to express on the surface of said membrane a monomeric polypeptide specific for a target associated with a tumor, wherein said monomeric polypeptide defines a naturally occurring motif.

### Claim 2 (depends on 1)

The T cell according to claim 1, wherein said target is selected from the group consisting of a target expressed by a tumor and a target associated with the tumor stroma.

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

The T cell according to claim 1 or 2, wherein said monomeric polypeptide is a lipocalin mutein

### Claim 4

A T cell modified to express and secrete a specific binding polypeptide, wherein said polypeptide is monomeric and is specific for an immunomodulatory target.

### Claim 5 (depends on 4)

The T cell according to claim 4, wherein said specific binding polypeptide is a scFv.

### Claim 6 (depends on 4)

The T cell according to claim 4, wherein said monomeric polypeptide defines a naturally occurring motif.

### Claim 7 (depends on 6)

The T cell according to claim 6, wherein said specific binding polypeptide is a lipocalin mutein.

### Claim 8 (depends on 4, 5, 6, 7)

The T cell according to any one of claims 4-7, wherein said immunomodulatory target is an immune checkpoint or costimulatory molecule.

### Claim 9 (depends on 4, 5, 6, 7, 8)

The T cell according to any one of claims 4-8, wherein said T cell secretes said specific binding polypeptide upon activation

### Claim 10 (depends on 4, 5, 6, 7, 8, 9)

The T cell according to any one of claims 4-9, which is modified to express on the surface of said membrane a monomeric polypeptide specific for a target associated with a tumor, wherein said monomeric polypeptide defines a naturally occurring motif.

### Claim 11 (depends on 10)

The T cell according to claim 10, wherein said target is selected from the group consisting of a target expressed by a tumor and a target associated with the tumor stroma.

### Claim 12 (depends on 10, 11)

The T cell according to claim 10 or 11, wherein said monomeric polypeptide is a lipocalin mutein.

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

A pharmaceutical composition comprising a T cell of any one of claims 1 to 12 and optionally a pharmaceutically acceptable carrier or excipient.

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

A T cell of any one of claims 1 to 12 for use in a method of treatment of cancer.

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

A method of treatment of cancer comprising administering to a subject in need thereof a pharmaceutically efficient amount or numbers of T cells of any one of claims 1 to 12.