# US 9,433,667 B2 · Cancer vaccines and vaccination methods

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- Number: US 9,433,667 B2
- Document ID: US9433667B2
- Status: Granted
- Kind: B2
- Application number: 13/327,125
- Filed: 2011-12-15
- Published: 2012-06-21
- Granted: 2016-09-06
- Earliest claimed: 2006-09-28
- Assignees: Cedars-Sinai Medical Center
- Applicants: John S. Yu; Gentao Liu; Keith L. Black
- Inventors: John S. Yu; Gentao Liu; Keith L. Black
- Web page: https://patentgrep.com/patent/US9433667B2

## CPC

- C12N 5/0639: {Dendritic cells, e.g. Langherhans cells in the epidermis}
- A61K 40/19: Dendritic cells
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/4205: {Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4}
- A61K 40/4217: {Receptors for interleukins [IL]}
- A61K 40/4245: {Tyrosinase or tyrosinase related proteinases [TRP-1 or TRP-2]}
- A61K 40/4268: {MAGE}
- A61K 40/4273: {Glycoprotein 100 [Gp100]}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/47: Brain; Nervous system
- C12N 2501/22: Colony stimulating factors (G-CSF, GM-CSF)
- C12N 2501/23: Interleukins [IL]
- C12N 2501/2304: Interleukin-4 (IL-4)
- C12N 2501/25: Tumour necrosing factors [TNF]
- C12N 2501/998: Proteins not provided for elsewhere
- C12N 2506/11: from blood or immune system 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

Methods and compositions for treating cancers (e.g., neural cancers) by dendritic cell vaccination are provided herein.

## Claims

### Claim 1

A composition comprising dendritic cells, wherein the dendritic cells present on human leukocyte antigen (HLA) on their surface peptide epitopes, wherein the peptide epitopes are each 9 to 13 amino acids length and comprise the following six amino acid sequences:
(SEQ ID NO: 3)
RSDSGQQARY from AIM-2;
(SEQ ID NO: 4)
EADPTGHSY from MAGE-1;
(SEQ ID NO: 5)
SVYDFFVWL from TRP-2;
(SEQ ID NO: 67)
IMDQVPFSV, a superagonist peptide from gp100;
(SEQ ID NO: 37)
VMAGVGSPYV from HER-2;
and
(SEQ ID NO: 8)
WLPFGFILI from IL-13 receptor α2,
wherein the dendritic cells acquired the peptide epitopes in vitro by exposure to synthetic peptides comprising the peptide epitopes.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the peptide epitopes comprise an HLA epitope from at least one antigen other than TRP-2, MAGE-1, HER-2, IL-13 receptor α2, gp100, and AIM2.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the composition comprises between 105 and 108 dendritic cells.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the composition comprises autologous dendritic cells.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the composition comprises allogeneic dendritic cells.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the dendritic cells present on HLA on their surface peptide epitopes of 9 or 10 amino acids in length.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the peptide epitopes consist of the following six amino acid sequences:
(SEQ ID NO: 3)
RSDSGQQARY from AIM-2;
(SEQ ID NO: 4)
EADPTGHSY from MAGE-1;
(SEQ ID NO: 5)
SVYDFFVWL from TRP-2;
(SEQ ID NO: 67)
IMDQVPFSV, a superagonist peptide from gp100;
(SEQ ID NO: 37)
VMAGVGSPYV from HER-2;
and
(SEQ ID NO: 8)
WLPFGFILI from IL-13 receptor α2.

### Claim 8

A process comprising:
obtaining bone marrow derived mononuclear cells from a patient,
culturing the mononuclear cells in vitro under conditions in which mononuclear cells become adherent to a culture vessel,
selecting a subset of the mononuclear cells comprising adherent cells,
culturing the adherent cells in the presence of one or more cytokines under conditions in which the cells differentiate into antigen presenting cells,
culturing the antigen presenting cells in the presence of synthetic peptides of the following six antigens: TRP-2, MAGE-1, HER-2, IL-13 receptor α2, gp100, and AIM2, wherein the synthetic peptides are each 9 to 13 amino acids in length and comprise the following six amino acid sequences:
(SEQ ID NO: 3)
RSDSGQQARY from AIM-2;
(SEQ ID NO: 4)
EADPTGHSY from MAGE-1;
(SEQ ID NO: 5)
SVYDFFVWL from TRP-2;
(SEQ ID NO: 67)
ITDQVPFSV, a superagonist peptide from gp100;
(SEQ ID NO: 37)
KIFGSLAFL from HER-2;
and
(SEQ ID NO: 8)
WLPFGFILI from IL-13 receptor α2,
under conditions in which the antigen presenting cells present the peptides on human leukocyte antigen (HLA), wherein the antigen presenting cells are dendritic cells.

### Claim 9 (depends on 8)

The process of claim 8, wherein the bone marrow derived cells are obtained from a patient with a glioma.

### Claim 10 (depends on 8)

The process of claim 8, wherein the antigen presenting cells are cultured in the presence of a synthetic peptide from at least one antigen other than TRP-2, MAGE-1, HER-2, IL-13receptor α2, gp100, and AIM2.