# US 2025/0084376 A1 · Ex vivo use of modified cells of leukemic origin for enhancing the efficacy of adoptive cell therapy

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- Number: US 2025/0084376 A1
- Document ID: US20250084376A1
- Status: Published application
- Kind: A1
- Application number: 18/804,310
- Filed: 2024-08-14
- Published: 2025-03-13
- Earliest claimed: 2020-03-27
- Assignees: Mendus B.V.
- Applicants: Mendus B.V.
- Inventors: Erik Hans Manting; Jeroen Rovers; Satwinder Kaur Singh
- Web page: https://patentgrep.com/patent/US20250084376A1

## 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 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/19: Dendritic cells
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/4243: {Wilms tumor 1 [WT1]}
- A61K 40/4269: {NY-ESO}
- A61K 40/428: {Undefined tumor antigens, e.g. tumor lysate or antigens targeted by cells isolated from tumor}
- A61K 40/46: Viral antigens
- A61P 35/00: Antineoplastic agents
- C12N 5/0639: {Dendritic cells, e.g. Langherhans cells in the epidermis}
- 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 2510/00: Genetically modified cells
- 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

## Abstract

The present disclosure provides ex vivo methods which employ modified cells of leukemic origin to enhance the efficacy of adoptive cell therapy.

## Claims

### Claim at position 1

1-123. (canceled)

### Claim 124

A method for generating and/or expanding a population of immune cells with enhanced activation status, comprising:
(a) obtaining a population of immune cells from a subject;
(b) contacting the population of immune cells with a non-proliferating modified cell of leukemic origin having a mature dendritic cell phenotype;
and
(c) co-culturing the population of immune cells and the modified cell of leukemic origin under conditions suitable to expand and stimulate proliferation of the immune cells,
thereby generating the population of immune cells with enhanced activation status, wherein the method results in multiplying the population of immune cells by at least 10 fold.

### Claim 125 (depends on 124)

The method of claim 124, wherein the modified cell of leukemic origin is CD40-positive, CD80-positive, and CD86-positive; and optionally wherein the modified cell of leukemic origin comprises a CD70 costimulatory molecule.

### Claim 126 (depends on 124)

The method of claim 124, wherein the modified cell of leukemic origin is a cell derived from cell line DCOne as deposited under the conditions of the Budapest treaty with the DSMZ under accession number DSMZ ACC3189 on 15 Nov. 2012.

### Claim 127 (depends on 124)

The method of claim 124, wherein the immune cells comprises memory T cells, memory B cells, and/or natural killer cells.

### Claim 128 (depends on 124)

The method of claim 124, wherein the population of immune cells are modified to express a chimeric antigen receptor (CAR) which binds a tumor antigen on a tumor cell in the patient.

### Claim 129 (depends on 124)

The method of claim 124, wherein the population of immune cells are obtained from a patient suffering from cancer.

### Claim 130 (depends on 129)

The method of claim 129, wherein the population of immune cells are obtained from peripheral blood mononuclear cells (PBMCs) of the patient suffering from a cancer.

### Claim 131 (depends on 124)

The method of claim 124, wherein the population of immune cells are obtained from a healthy donor subject.

### Claim 132 (depends on 124)

The method of claim 124, wherein the population of immune cells comprise T cells.

### Claim 133 (depends on 132)

The method of claim 132, wherein T cells are obtained from circulating blood of an individual.

### Claim 134 (depends on 132)

The method of claim 132, wherein the population of T cells comprise both CD4+ and CD8+ cells, and the method results in an increased ratio of CD4+ to CD8+ cells.

### Claim 135 (depends on 132)

The method of claim 132, wherein the increased ratio of CD4+ to CD8+ cells is between at or about 1:5 and at or about 5:1.

### Claim 136 (depends on 132)

The method of claim 132, wherein the increased ratio of CD4+ to CD8+ cells is between at or about 1:3 and at or about 3:1.

### Claim 137 (depends on 124)

The method of claim 124, wherein the modified cell of leukemic origin comprises an exogenous antigen or peptide fragments of the exogenous antigen, wherein the exogenous antigen is a tumor-associated antigen (TAA) or non-tumor-associated antigen.

### Claim 138 (depends on 137)

The method of claim 137, wherein the modified cell of leukemic origin is loaded with the exogenous antigen or peptide fragments thereof prior to its exhibiting a mature dendritic cell phenotype, during transition of the modified cell of leukemic origin to a mature dendritic cell phenotype, or after the modified cell of leukemic origin exhibits a mature dendritic cell phenotype.

### Claim 139 (depends on 124)

The method of claim 124, wherein the population of immune cells are modified to express a chimeric antigen receptor (CAR) which binds the exogenous antigen or peptide fragments thereof displayed on the modified cell of leukemic origin.

### Claim 140 (depends on 124)

A method for treating a patient suffering from the cancer, and the method comprising administering to the patient suffering from the cancer the population of immune cells with enhanced activation status generated and expanded by the method of claim 124.

### Claim 141 (depends on 140)

The method of claim 140, wherein the population of immune cells with enhanced activation status are autologous to the patient that is administered the immune cells.

### Claim 142 (depends on 140)

The method of claim 140, wherein the cancer comprises a liquid tumor.

### Claim 143 (depends on 140)

The method of claim 140, wherein the cancer comprises a solid tumor.