# US 10,946,042 B2 · Compositions and methods for selective phagocytosis of human cancer cells

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- Number: US 10,946,042 B2
- Document ID: US10946042B2
- Status: Granted
- Kind: B2
- Application number: 15/366,844
- Filed: 2016-12-01
- Published: 2017-06-01
- Granted: 2021-03-16
- Earliest claimed: 2015-12-01
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: Dennis E. Discher; Kyle R. Spinler; Cory Alvey
- Web page: https://patentgrep.com/patent/US10946042B2

## CPC

- C12N 5/0645: {Macrophages, e.g. Kuepfer cells in the liver; Monocytes}
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 40/10: characterised by the cell type used
- A61K 40/17: Monocytes; Macrophages
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/4202: {Receptors, cell surface antigens or cell surface determinants}
- A61K 40/4204: {Epidermal growth factor receptors [EGFR]}
- A61K 40/4257: {Mucins, e.g. MUC-1}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 49/0041: {Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal (in vivo G01N)}
- A61K 49/0097: {Cells, viruses, ghosts, red blood cells, viral vectors, used for imaging or diagnosis in vivo}
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/55: Lung
- 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)

## Abstract

The present invention relates to compositions and methods that provide novel therapies in cancer. The invention includes a phagocytic cell modified with a repressor of signal regulatory protein-alpha (SIRPα) and bound to a targeting antibody to enhance phagocytic activity of the phagocytic cell toward tumor tissue. Methods of enhancing phagocytic activity and treating a tumor are also included.

## Claims

### Claim 1

A composition comprising a modified macrophage comprising a repressor of signal regulatory protein-alpha (SIRPα), and a pharmaceutically acceptable carrier;
wherein the repressor of SIRPα is selected from the group consisting of a SE7C2 antibody and a P84 antibody; and
wherein the macrophage is bound to a MA5-15131 targeting antibody and possesses phagocytic activity against tumor tissue.

### Claim 2 (depends on 1)

The modified macrophage of claim 1, wherein the targeting antibody is bound to a Fc receptor on the macrophage.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the composition has a therapeutic effect on tumor tissue.

### Claim 4

A composition comprising a signal regulatory protein-alpha (SIRPα) repressed bone marrow cell bound to a targeting antibody; and a pharmaceutically acceptable carrier;
wherein the repressor of SIRPα is selected from the group consisting of a SE7C2 antibody and a P84 antibody; and
wherein the bone marrow cell is bound to a MA5-15131 targeting antibody and possesses phagocytic activity against tumor tissue.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the targeting antibody is bound to a Fc receptor on the bone marrow cell.

### Claim 6 (depends on 4)

The composition of claim 4, wherein the composition has a therapeutic effect on tumor tissue.

### Claim 7 (depends on 6)

The composition of claim 6, wherein the therapeutic effect comprises tumor shrinkage of at least 60% of the tumor.

### Claim 8 (depends on 6)

The composition of claim 6, wherein the tumor tissue comprises a brain cancer, bladder cancer, breast cancer, cervical cancer, colorectal cancer, liver cancer, kidney cancer, lymphoma, leukemia, lung cancer, melanoma, metastatic melanoma, mesothelioma, neuroblastoma, ovarian cancer, prostate cancer, gastric cancer, pancreatic cancer, renal cancer, skin cancer, thymoma, sarcoma, non-Hodgkin's lymphoma, Hodgkin's lymphoma, or uterine cancer.

### Claim 9 (depends on 4)

A method of enhancing phagocytic activity of a phagocytic cell toward MUC1 expressing tumor tissue in a mammal, the method comprising administering to the mammal an effective amount of the composition of claim 4, wherein the effective amount of the composition provides an SIRPα repressed bone marrow cell bound to a MUC1 targeting antibody, and wherein the effective amount enhances phagocytic activity and has a therapeutic effect in the mammal.

### Claim 10 (depends on 9)

The method of claim 9, wherein the SIPRα repressed bone marrow cell differentiates into a mature macrophage.

### Claim 11 (depends on 9)

The method of claim 9, wherein the therapeutic effect comprises tumor tissue shrinkage of at least 60% of the tumor tissue.

### Claim 12 (depends on 9)

The method of claim 9, wherein the macrophage is bound to the MUC1 targeting antibody through an Fc receptor on the macrophage.

### Claim 13 (depends on 4, 9)

The method of claim 9, wherein the composition of claim 4 is administered intravenously to the mammal.

### Claim 14 (depends on 9)

The method of claim 9, wherein the mammal is a human.

### Claim 15 (depends on 1)

A method of enhancing phagocytic activity of a phagocytic cell toward MUC1 expressing tumor tissue in a mammal, the method comprising administering to the mammal an effective amount of the composition of claim 1, wherein the effective amount of the composition provides an SIRPα repressed macrophage bound to a MUC1 targeting antibody, and wherein the effective amount enhances phagocytic activity and has a therapeutic effect in the mammal.

### Claim 16 (depends on 1, 15)

The method of claim 15, wherein the composition of claim 1 is administered intravenously to the mammal.

### Claim 17 (depends on 15)

The method of claim 15, wherein the mammal is a human.

### Claim 18 (depends on 1)

A method of treating a MUC1 expressing tumor in a mammal, the method comprising administering to the mammal an effective amount of the composition of claim 1, wherein the effective amount of the composition provides an SIRPα repressed macrophage bound to a MUC1 targeting antibody, and wherein the effective amount of the composition has a therapeutic effect in the mammal, thereby treating the MUC1 expressing tumor tissue.

### Claim 19 (depends on 18)

The method of claim 18, wherein the therapeutic effect comprises tumor tissue shrinkage of at least 60% of the tumor tissue.

### Claim 20 (depends on 18)

The method of claim 18, wherein the macrophage is bound to the MUC1 targeting antibody through an Fc receptor on the macrophage.

### Claim 21 (depends on 1, 18)

The method of claim 18, wherein the composition of claim 1 is administered intravenously to the mammal.

### Claim 22 (depends on 18)

The method of claim 18, wherein the mammal is a human.

### Claim 23 (depends on 4)

A method of treating a MUC1 expressing tumor in a mammal, the method comprising administering to the mammal an effective amount of the composition of claim 4, wherein the effective amount of the composition provides an SIRPα repressed bone marrow cell bound to a MUC1 targeting antibody, and wherein the effective amount of the composition has a therapeutic effect in the mammal, thereby treating the MUC1 expressing tumor tissue.

### Claim 24 (depends on 23)

The method of claim 23, wherein the SIPRα repressed bone marrow cell differentiates into a mature macrophage.

### Claim 25 (depends on 23)

The method of claim 23, wherein the bone marrow cell is bound to the MUC1 targeting antibody through an Fc receptor on the bone marrow cell.

### Claim 26 (depends on 4, 23)

The method of claim 23 wherein the composition of claim 4 is administered intravenously to the mammal.

### Claim 27 (depends on 23)

The method of claim 23 wherein the mammal is human.

### Claim 28 (depends on 23)

The method of claim 23, wherein the therapeutic effect comprises tumor tissue shrinkage of at least 60% of the tumor tissue.

### Claim 29 (depends on 1)

A method of modifying macrophage activity to target a MUC1 expressing tissue in a mammal, the method comprising contacting a macrophage cell with the composition of claim 1 to provide a target antibody loaded modified macrophage having modified macrophage activity, wherein the modified macrophage has enhanced phagocytic activity and a therapeutic effect on the targeted tissue in the mammal.

### Claim 30 (depends on 29)

The method of claim 29, wherein the modified macrophage has a stronger phagocytic activity than a native macrophage of the mammal.

### Claim 31 (depends on 4)

A method of modifying phagocytic activity to target a MUC1 expressing tissue in a mammal, the method comprising contacting a bone marrow cell with the composition of claim 4 to provide a target antibody loaded modified bone marrow cell having modified phagocytic activity, wherein the modified bone marrow cell has enhanced phagocytic activity and a therapeutic effect on the targeted tissue in the mammal.

### Claim 32 (depends on 31)

The method of claim 31, wherein the target antibody loaded modified bone marrow cell differentiates into a mature macrophage.

### Claim 33 (depends on 1)

A method of modulating phagocytic activity to target a MUC1 expressing tissue in a mammal, the method comprising administering to the mammal and effective amount of the composition of claim 1 and an opsonin, wherein the effective amount of the composition of claim 1 modulates phagocytic activity and has a therapeutic effect on the targeted tissue in the mammal.

### Claim 34 (depends on 4)

A method of modulating phagocytic activity to target a MUC1 expressing tissue in a mammal, the method comprising administering to the mammal and effective amount of the composition of claim 4 and an opsonin, wherein the effective amount of the composition of claim 4 modulates phagocytic activity and has a therapeutic effect on the targeted tissue in the mammal.

### Claim 35 (depends on 1)

A method of treating a MUC1 expressing tumor in a mammal, the method comprising administering to the mammal an effective amount of the composition of claim 1 and an opsonin, thereby treating the tumor tissue.

### Claim 36 (depends on 4)

A method of treating a MUC1 expressing tumor in a mammal, the method comprising administering to the mammal an effective amount of the composition of claim 4 and an opsonin, thereby treating the tumor tissue.