# US 2019/0167722 A1 · Transfection of dendritic cells and methods therefor

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- Number: US 2019/0167722 A1
- Document ID: US20190167722A1
- Status: Published application
- Kind: A1
- Application number: 16/322,310
- Filed: 2017-08-02
- Published: 2019-06-06
- Earliest claimed: 2016-08-02
- Assignees: Nant Holdings IP, LLC; NantCell, Inc.
- Applicants: Nant Holdings IP, LLC; Nantcell, Inc.
- Inventors: Patrick Soon-Shiong; Kayvan Niazi
- Web page: https://patentgrep.com/patent/US20190167722A1

## CPC

- 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 35/15: Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells (presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00)
- A61K 38/2013: {IL-2}
- A61K 38/2046: {IL-7}
- A61K 38/208: {IL-12}
- A61K 38/2086: {IL-13 to IL-16}
- A61K 40/19: Dendritic cells
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/36: Immune checkpoint inhibitors
- A61K 40/42: Cancer antigens
- A61P 35/00: Antineoplastic agents
- C12N 5/0635: {B lymphocytes}
- C12N 5/0636: {T lymphocytes}
- C12N 5/0639: {Dendritic cells, e.g. Langherhans cells in the epidermis}
- C12N 2502/1107: B cells
- C12N 2502/1114: T cells
- C12N 2502/1121: Dendritic cells
- C12N 2502/1157: Monocytes, macrophages
- C12N 2502/1164: NK cells
- C12N 2510/00: Genetically modified cells
- C12N 2710/10343: viral genome or elements thereof as genetic vector
- 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

Immunotherapeutic methods and compositions are contemplated where one or more neoepitopes and/or tumor associated antigens are produced in, or delivered to dendritic cells, and in which so modified dendritic cells are co-cultured with immune competent cells of a patient, preferably in the presence of stimulatory signals. Cells are then transfused to the patient that has preferably undergone immune checkpoint inhibition treatment.

## Claims

### Claim 1

A method of treating a patient having a tumor, comprising:
administering to the patient a plurality of immune competent cells that were previously ex vivo exposed to transfected antigen-presenting cells;
wherein the antigen-presenting cells were transfected with at least one patient-specific tumor neoepitope or an RNA or expression vector comprising a nucleic acid sequence that encodes the at least one patient-specific tumor neoepitope; and
wherein the immune competent cells are obtained from the patient having the tumor.

### Claim 2

(canceled)

### Claim 3 (depends on 1)

The method of claim 1 wherein the plurality of immune competent cells are enriched in at least one of a CD4+ T-cell, a CD8+ T-cell, an NK cell, a macrophage, a monocyte, and a B- cell.

### Claim at position 4

4-7. (canceled)

### Claim 8 (depends on 1)

The method of claim 1 wherein the at least one patient-specific tumor neoepitope is an HLA-matched patient-specific tumor neoepitope.

### Claim 9 (depends on 1)

The method of claim 1 wherein the at least patient-specific tumor neoepitope further comprises a targeting sequence that targets the patient-specific tumor neoepitope to MHC-I or MHC-II presentation.

### Claim 10

(canceled)

### Claim 11 (depends on 1)

The method of claim 1 wherein the antigen-presenting cells were further transfected with or exposed to at least one of an immune stimulating molecule, a nucleic acid encoding at least one immune stimulating molecule, a checkpiont inhibitor, or a nucleic acid encoding at least one checkpoint inhibitor.

### Claim at position 9

12-18. (canceled)

### Claim 19 (depends on 1)

The method of claim 1 wherein the plurality of immune competent cells were exposed to the transfected antigen-presenting cells in the presence of a cytokine.

### Claim 20

(canceled)

### Claim 21 (depends on 1)

The method of claim 1 further comprising a step of administering to the patient an immune checkpoint inhibitor before the step of administering the plurality of immune competent cells.

### Claim at position 13

22-23. (canceled)

### Claim 24

A method of ex vivo activating immune competent cells from a patient having a tumor, comprising:
obtaining from the patient a plurality of immune competent cells;
transfecting ex vivo a plurality of antigen-presenting cells with at least one patient-specific tumor neoepitope or with an expression vector comprising a nucleic acid that encodes the at least one patient-specific tumor neoepitope; and
co-culturing the plurality of immune competent cells with the plurality of transfected antigen-presenting cells for a time sufficient to activate the immune competent cells.

### Claim 25

(canceled)

### Claim 26 (depends on 24)

The method of claim 24 wherein the plurality of immune competent cells are enriched in at least one of a CD4+ T-cell, a CD8+ T-cell, an NK cell, a macrophage, a monocyte, and a B-cell.

### Claim at position 17

27-30. (canceled)

### Claim 31

The method of claim wherein the at least one patient-specific tumor neoepitope is an HLA-matched patient-specific tumor neoepitope.

### Claim 32 (depends on 24)

The method of claim 24 wherein the at least one patient-specific tumor neoepitope further comprises a targeting sequence that targets the tumor-related epitope to MHC-I or MHC-II presentation.

### Claim 33

(canceled)

### Claim 34 (depends on 24)

The method of claim 24 wherein the antigen-presenting cells were further transfected with or exposed to at least one of an immune stimulating molecule, a nucleic acid encoding at least one immune stimulating molecule, a checkpoint inhibitor, or a nucleic acid encoding at least one checkpoint inhibitor.

### Claim at position 22

35-41. (canceled)

### Claim 42 (depends on 24)

The method of claim 24 wherein the step of co-culturing is performed in the presence of a cytokine.

### Claim at position 24

43-44. (canceled)

### Claim 45

A pharmaceutical composition, comprising:
a pharmaceutically acceptable carrier for transfusion in combination with a plurality of immune competent cells and a plurality of transfected antigen-presenting cells;
wherein the antigen-presenting cells are cells transfected with at least one patient-specific tumor neoepitope or an expression vector comprising a nucleic acid that encodes the at least one patient-specific tumor neoepitope; and
wherein the immune competent cells are obtained from the patient having the tumor.

### Claim 46

(canceled)

### Claim 47 (depends on 45)

The composition of claim 45 wherein the plurality of immune competent cells are enriched in at least one of a CD4+ T-cell, a CD8+ T-cell, an NK cell, a macrophage, a monocyte, and a B-cell.

### Claim at position 28

48-51. (canceled)

### Claim 52 (depends on 45)

The composition of claim 45 wherein the at least one patient-specific tumor neoepitope is an HLA-matched tumor-related epitope.

### Claim 53 (depends on 45)

The composition of claim 45 wherein the at least one patient-specific tumor neoepitope further comprises a targeting sequence that targets the tumor-related epitope to MHC-I or MHC-II presentation.

### Claim 54

(canceled)

### Claim 55 (depends on 45)

The composition of claim 45 wherein the antigen-presenting cells were further transfected with or exposed to at least one of an immune stimulating molecule, a nucleic acid encoding at least one immune stimulating molecule, a checkpoint inhibitor, or a nucleic acid encoding at least one checkpoint inhibitor.

### Claim at position 33

56-62. (canceled)

### Claim 63 (depends on 45)

The composition of claim 45 further comprising a cytokine or an immune checkpoint inhibitor.

### Claim 64 (depends on 63)

The composition of claim 63 wherein cytokine is IL-2, IL-7, IL-12, IL-15, or a IL-15 superagonist.

### Claim at position 36

65-85. (canceled)