# US 2014/0193449 A1 · Compositions and methods for cancer treatment

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- Number: US 2014/0193449 A1
- Document ID: US20140193449A1
- Status: Published application
- Kind: A1
- Application number: 14/149,911
- Filed: 2014-01-08
- Published: 2014-07-10
- Earliest claimed: 2007-05-04
- Assignees: University Health Network
- Applicants: University Health Network
- Inventors: Jeffrey A. Medin; Andrea McCart; Severine Loisel-Meyer
- Web page: https://patentgrep.com/patent/US20140193449A1

## CPC

- C12N 15/86: Viral vectors
- A01K 67/0275: Genetically modified vertebrates, e.g. transgenic
- A61K 38/208: {IL-12}
- A61K 39/0011: {Cancer antigens}
- A61K 39/001106: {Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4}
- A61K 39/001182: {Carcinoembryonic antigen [CEA]}
- A61K 39/21: Retroviridae, e.g. equine infectious anemia virus
- A61K 40/19: Dendritic cells
- A61K 40/22: Immunosuppressive or immunotolerising
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/34: Antigenic peptides
- A61K 40/416: {Antigens related to auto-immune diseases; Preparations to induce self-tolerance}
- A61K 40/4205: {Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ ErbB4}
- A61K 40/4266: {Carcinoembryonic antigen [CEA]}
- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- C07K 14/5434: {IL-12}
- C07K 14/70503: {Immunoglobulin superfamily}
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/8509: {for producing genetically modified animals, e.g. transgenic}
- A01K 2207/15: Humanized animals
- A01K 2217/00: Genetically modified animals
- A01K 2227/105: Murine
- A01K 2267/0331: Animal model for proliferative diseases
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/53: {DNA (RNA) vaccination}
- A61K 2039/55522: {Cytokines; Lymphokines; Interferons}
- A61K 2039/55538: {IL-12}
- A61K 2039/57: {characterised by the type of response, e.g. Th1, Th2}
- A61K 2039/575: {humoral response}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- C07K 2319/06: containing a lysosomal/endosomal localisation signal
- C12N 2740/15021: Viruses as such, e.g. new isolates, mutants or their genomic sequences
- C12N 2740/15034: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
- C12N 2740/15043: viral genome or elements thereof as genetic vector
- C12N 2740/15071: Demonstrated in vivo effect
- C12N 2740/16043: viral genome or elements thereof as genetic vector
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- 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
- 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)

## Abstract

Compositions and methods for delivering tumor associated antigens and immune modulatory molecules to result in a therapeutic effect are disclosed. The compositions and methods use stably integrating lentiviral delivery systems. The methods are useful for therapeutically and prophylactically treating cancer such as colon cancer.

## Claims

### Claim 1

A composition, vector construct or virus comprising:
a stably integrating delivery vector;
a tumor associated antigen cassette;
a lysomal targeting cassette;
wherein the lysosomal targeting cassette is operatively linked to the tumor associated antigen cassette.

### Claim 2 (depends on 1)

The composition, vector construct or virus of claim 1, wherein the delivery vector comprises a retroviral vector, optionally a lentiviral vector, wherein the lentiviral vector comprises one or more of a: 5′-Long terminal repeat (LTR), HIV signal sequence, HIV Psi signal 5′-splice site (SD), delta-GAG element, Rev Responsive Element (RRE), 3′-splice site (SA), Elongation factor (EF) 1-alpha promoter and 3′-Self inactivating LTR (SIN-LTR).

### Claim 3

(canceled)

### Claim 4 (depends on 2)

The composition, vector construct or virus of claim 2, wherein the lentiviral vector comprises a central polypurine tract and/or a woodchuck hepatitis virus post-transcriptional regulatory element; optionally wherein the cPPT comprises SEQ ID NO:2 and/or the WPRE comprises SEQ ID NO:3; or, optionally wherein the cPPT comprises at least 70% sequence identity to SEQ ID NO:2 and/or a the WPRE comprises at least 70% sequence identity to SEQ ID NO:3, wherein the lentiviral vector comprises the nucleotides corresponding to a pHR′ vector backbone.

### Claim 5

(canceled)

### Claim 6

(canceled)

### Claim 7 (depends on 1)

The composition, vector construct or virus of claim 1, wherein the tumor associated antigen cassette comprises all or part of a carcinoembryonic antigen polynucleotide or wherein the tumor associated antigen cassette comprises all or part of a HER-2/neu polynucleotide.

### Claim at position 8

8-10. (canceled)

### Claim 11 (depends on 1)

The composition, vector construct or virus of claim 1, wherein the lysosomal targeting cassette comprises a LAMP1 lysosomal targeting polynucleotide, wherein the LAMP1 lysosomal targeting polynucleotide is selected from the group consisting of SEQ ID NO:1 or a polynucleotide having at least 70% sequence identity to SEQ ID NO:1 which maintains lysosomal targeting activity.

### Claim 12

(canceled)

### Claim 13 (depends on 1)

The composition, vector construct or virus of claim 1, further comprising an activator polynucleotide encoding a polypeptide that converts a prodrug to a drug, optionally a modified tmpk polynucleotide and/or a tmpk polynucleotide with at least 80% sequence identity to a modified tmpk polynucleotide described herein, and optionally further comprising a detection cassette.

### Claim 14

(canceled)

### Claim 15 (depends on 13)

The composition, vector construct or virus of claim 13, wherein the detection cassette is selected from CD19, truncated CD19, CD20, human CD24, murine HSA, human CD25 (huCD25), a truncated form of low affinity nerve growth factor receptor (LNGFR), truncated CD34 or erythropoietin receptor (EpoR) polynucleotides and/or a polynucleotide comprising at least 70% sequence identity to a CD19, truncated CD19, CD20, human CD24, murine HSA, CD25, a truncated form of low affinity nerve growth factor receptor (LNGFR), truncated CD34 or erythropoietin receptor (EpoR)polynucleotide.

### Claim 16 (depends on 1, 5)

The composition, vector construct or virus of claims 1-1-5, further comprising an immune modulatory cassette, wherein the immune modulatory cassette comprises a polynucleotide selected from the group comprising IL-12 p35, IL-12 p40, IL-12 fusion, IL-15, RANKL, CD40L, IFNγ and TNFα polynucleotides and combinations thereof, or wherein the immune modulatory cassette encodes a protein that modulates dendritic cells, encodes a protein that modulates T cells, optionally CD4+ T cells.

### Claim at position 15

17-20. (canceled)

### Claim 21 (depends on 20)

The composition, vector construct or virus of claim 20, wherein the IL-12 polynucleotide is a mammalian IL-12 polynucleotide, or wherein the IL-12 polynucleotide comprises at least 70% sequence identity to sequences having SEQ ID NO:16-19.

### Claim at position 17

22-25. (canceled)

### Claim 26 (depends on 1)

A cell transduced with the composition claim 1 vector construct, or the virus of claim 1, wherein the cell is optionally an antigen presenting cell, a stem cell, immune cell, hematopoietic cell, dendritic cell, or an immature dendritic cell and/or a population of cells comprising the transduced cell.

### Claim 27 (depends on 1)

A method of expressing a tumor associated antigen in a mammalian cell comprising contacting the mammalian cell with the composition vector construct, or virus of claim 1, optionally wherein the mammalian cell is selected from a stem cell, an immune cell, a hematopoietic cell, an antigen presenting cell, a cancer cell and a dendritic cell.

### Claim at position 20

28-32. (canceled)

### Claim 33 (depends on 27)

The method of claim 27, further comprising a step of treating the transduced cell with a cell maturing agent, wherein the cell maturing agent is TNFα.

### Claim 34

(canceled)

### Claim 35 (depends on 27)

The method of claim 27, further comprising a step of isolating the transduced cells, and/or further comprising a step wherein the isolated mammalian cells are transplanted in a mammal.

### Claim 36

(canceled)

### Claim 37 (depends on 1)

A method of treating a subject in need thereof, optionally a subject with cancer or an increased risk of developing cancer, comprising administering to the subject in need thereof the composition, vector construct, or virus of claim 1.

### Claim 38 (depends on 26)

A method of treating a subject in need thereof comprising administering to the subject in need thereof the tranduced cell or population of claim 26.

### Claim 39

(canceled)

### Claim 40 (depends on 4)

A method of reducing cancer burden in a subject having a CEA or HER-2/neu positive cancer comprising administering to the subject the composition of, vector construct, or virus of claim 4, or a transduced cell or population of cells comprising the composition, vector construct or virus.

### Claim 41

(canceled)

### Claim 42

(canceled)

### Claim 43 (depends on 37)

The method of claim 37, wherein the cancer is colon cancer, rectal cancer, stomach cancer, pancreatic cancer, non-small cell lung cancer, metastatic pancreatic cancer, ovarian cancer or breast cancer.

### Claim 44 (depends on 38)

The method of claim 38, wherein the transduced cell is a dendritic cell, an immature dendritic cell, or an autologous dendritic cell.

### Claim 45

(canceled)

### Claim 46

(canceled)

### Claim 47 (depends on 1)

A method of inducing or enhancing an immune response in a subject in need thereof comprising administering to the subject in need thereof the composition, vector construct, the virus of claim 1, or a transduced cell or population of cells comprising the composition, vector construct or virus.

### Claim 48

(canceled)

### Claim 49

(canceled)

### Claim 50 (depends on 38)

The method of claim 38 wherein the transduced cell or population is growth arrested or irradiated prior to administering to the subject.

### Claim at position 39

51-68. (canceled)

### Claim 69 (depends on 38)

The method of claim 38, wherein the number of cells administered ranges from 105 cells to 109 cells, optionally about 105 cells, about 106 cells, about 107, cells, about 108 cells, or about 109 cells.

### Claim 70

(canceled)