Methods for manipulating phagocytosis mediated by CD47

• US 9,493,575 B2
• Filed: 07/14/2015
• Issued: 11/15/2016
• Est. Priority Date: 01/15/2008
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Jaiswal, Siddhartha, Weissman, Irving L., Majeti, Ravindra, Chao, Mark P.
• Primary Examiner(s): CANELLA, KAREN A
• Application Number:
  US14/799,328
• Publication Number:
  US 20160009814A1
• Time in Patent Office: 490 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61K 47/6861 the tumour determinant being from kidney or bladder cancer cell
• CPC Class Codes: A61K 47/6863 the tumour determinant being from stomach or intestines cancer cell
• CPC Class Codes: A61K 47/6865 the tumour determinant being from skin, nerves or brain cancer cell
• CPC Class Codes: A61K 47/6867 the tumour determinant being from a cell of a blood cancer
• CPC Class Codes: A61K 47/6869 the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/3038 : Kidney, bladder
• CPC Class Codes: C07K 16/3046 : Stomach, Intestines
• CPC Class Codes: C07K 16/3053 : Skin, nerves, brain
• CPC Class Codes: C07K 16/3061 : Blood cells
• CPC Class Codes: C07K 16/3069 : Reproductive system, e.g. ovaria, uterus, testes, prostate
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 : multispecific
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/75 : Agonist effect on antigen
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C12N 5/0093 : Purging against cancer cells
• CPC Class Codes: C12N 5/0694 : Cells of blood, e.g. leukemia cells, myeloma cells
• CPC Class Codes: C12Q 1/6886 : for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/112 : Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/136 : Screening for pharmacological compounds
• CPC Class Codes: G01N 2500/04 : Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 33/5011 : for testing antineoplastic activity
• CPC Class Codes: G01N 33/57426 : leukemia

Abstract

Methods are provided to manipulate phagocytosis of cancer cells, including e.g. leukemias, solid tumors including carcinomas, etc.

Claims

1. A method of increasing the elimination of hematopoietic cancer cells by phagocytosis in a human subject comprising:

administering to the subject a first monoclonal antibody specific for a marker of the cancer cells other than CD47 which comprises an Fc region capable of engaging Fc receptors on phagocytic cells to signal phagocytosis of the hematopoietic cancer cells, and a second monoclonal antibody that prevents the binding of CD47 to SIRP alpha and increases phagocytosis of the hematopoietic cancer cells by the first antibody.

2. The method of claim 1, wherein the first monoclonal antibody is an entire humanized, chimeric or human antibody.

3. The method of claim 1, wherein the first monoclonal antibody specifically binds to an AML stem cell surface marker.

4. The method of claim 1, wherein the hematopoietic cancer cells are AML cells.

5. The method of claim 1, wherein the second monoclonal antibody is an antibody that specifically binds to CD47.

6. The method of claim 1, wherein the second monoclonal antibody is an entire antibody.

7. The method of claim 1, wherein the second monoclonal antibody is a binding fragment.