# US 12,215,158 B2 · CD1a antibody-expressing CAR T-cells for the treatment of CD1a-positive cancer

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- Number: US 12,215,158 B2
- Document ID: US12215158B2
- Status: Granted
- Kind: B2
- Application number: 17/430,705
- Filed: 2020-02-13
- Published: 2022-05-12
- Granted: 2025-02-04
- Earliest claimed: 2019-02-14
- Assignees: FundacíOn Instituto De InvestigacíOn Contra La Leucemia Josep Carreras (Ijc); Institució Catalana De Recerca I Estudis Avanats (Icrea); Fundació Institut D'Investigació En Ciencies De La Salut Germans Trias I Pujol (Igtp)
- Applicants: FundacióN Instituto De InvestigacióN Contra La Leucemia Josep Carreras (Ijc); Institució Catalana De Recerca I Estudis Avanç ̧Ats (Icrea); Fundació Institut D'Investigació En Ciencies De La Salut Germans Trias I Pujol (Igtp)
- Inventors: Pablo Menéndez Buján; Diego Sanchez Martínez; Clara Bueno Uroz; Francisco Gutiérrez Agüera; Heleia Roca-Ho
- Web page: https://patentgrep.com/patent/US12215158B2

## CPC

- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- 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 40/4224: {Molecules with a "CD" designation not provided for elsewhere}
- A61P 35/00: Antineoplastic agents
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- 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
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- 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
- 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)
- 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)

## Abstract

Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. The extension of chimeric antigen receptor T-cells (CARTs) to T-ALL remains challenging because the shared expression of target antigens between CARTs and T-ALL blasts leads to CARTs fratricide. CD 1a is exclusively expressed in cortical T-ALLs, a major subset of T-ALL. The expression of CD 1a is restricted to cortical thymocytes and neither CD34+ progenitors nor T-cells express CD 1a during ontogeny, confining the risk of on-target/off-tumor toxicity. The present invention provides CARs comprising a CD 1a-targeting moiety which may be transduced or transformed into T cells. The resultant CARTs are suitable for the treatment of cortical T-ALLs.

## Claims

### Claim 1

A method of treating a CD 1a-positive cancer in a subject in need thereof, said method comprising administering to said subject a CD1a-negative allo-tolerant T cell comprising a nucleic acid encoding a chimeric antigen receptor (CAR) comprising:
(i) an extracellular domain comprising a CD 1a targeting-moiety, wherein the CD 1a targeting moiety is an antibody, scFv, Fab, or scFab comprising a VL domain and VH domain,
wherein said VL domain comprises LCDR1, LCDR2 and LCDR3 polypeptides and said VH domain comprises HCDR1, HCDR2 and HCDR3 polypeptides, and LCDR1 consists of QDINKY (SEQ ID NO: 1), LCDR2 consists of YTS, LCDR3 consists of LHYDNLPWT (SEQ ID NO: 3), HCDR1 consists of GYAFSTYT (SEQ ID NO: 4), HCDR2 consists of INPNSAST (SEQ ID NO: 5), and HCDR3 consists of ARGFYTMDY (SEQ ID NO: 6);
(ii) a transmembrane domain; and
(iii) an intracellular signaling domain.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the transmembrane domain comprises the transmembrane domain of CD28, CD3, CD45, CD4, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD 137, or CD154.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the transmembrane domain comprises the transmembrane domain of CD8.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the intracellular signaling domain comprises the intracellular domain of CD3ξ, FcRγ, CD3γ, CD3δ, CD3ε, CD5, CD22, CD79a, CD79b or CD66b.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the intracellular signaling domain comprises the intracellular domain of CD3ξ.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the CAR further comprises a costimulatory signaling domain.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the costimulatory signaling domain comprises the intracellular domain of CD27, CD28, CD137, CD134, CD30, CD40, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, CD278 or CD276.

### Claim 8 (depends on 7)

The method according to claim 7, wherein the costimulatory signaling domain comprises the intracellular domain of CD137.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the CD 1a-positive cancer is cortical T-cell acute lymphoblastic leukemia.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the CD 1a-positive cancer is relapsed/refractory cortical T-cell acute lymphoblastic leukemia.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the CD 1a-positive cancer is CD 1a+ T-cell lymphoblastic lymphoma.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the CD 1a-positive cancer is relapsed/refractory CD1a+ T-cell lymphoblastic lymphoma.

### Claim 13 (depends on 1)

A method of treating a CD 1a-positive cancer in a subject in need thereof, said method comprising administering to said subject a pharmaceutical composition comprising a plurality of T cells as defined in claim 1 and a pharmaceutically acceptable carrier or diluent.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the CD 1a-positive cancer is cortical T-cell acute lymphoblastic leukemia.

### Claim 15 (depends on 14)

The method according to claim 14, wherein the CD 1a-positive cancer is relapsed/refractory cortical T-cell acute lymphoblastic leukemia.

### Claim 16 (depends on 13)

The method according to claim 13, wherein the CD 1a-positive cancer is CD1a+ T-cell lymphoblastic lymphoma.

### Claim 17 (depends on 16)

The method according to claim 16, wherein the CD 1a-positive cancer is relapsed/refractory CD1a+ T-cell lymphoblastic lymphoma.