Methods to improve cell therapy

Patent metadata

Field	Value
Publication number	US-2016184367-A1
Application number	US-201514982863-A
Country	US
Kind code	A1
Filing date	Dec 29, 2015
Priority date	Dec 30, 2014
Publication date	Jun 30, 2016
Grant date	—

Abstract

Methods of treatment are provided herein, including administration of a population cells modified to enforce expression of an E-selectin and/or an L-selectin ligand, the modified cell population having a cell viability of at least 70% after a treatment to enforce such expression.

First claim

1 . A method of enhancing cell delivery into a target tissue of a subject and/or enhancing tissue colonization in the target tissue of the subject, the method comprising:
administering to the subject a population of cells that express an E-selectin ligand and/or an L-selectin ligand, the population expressing the E-selectin ligand and/or L-selectin ligand at a level that exceeds the level of expression of a native population of the cells, wherein said cell administration occurs coincident with E-selectin expression on endothelial cells within the target tissue and/or coincident with accumulation of leukocytes within the target tissue.

2 . A method of treating a disease, disorder or medical condition manifesting as inflamed and/or damaged tissue in a subject, the method comprising:
administering to the subject a population of cells that express an E-selectin ligand and/or an L-selectin ligand, the population expressing the E-selectin ligand and/or L-selectin ligand at a level that exceeds the level of expression of a native population of the cells, wherein said cell administration occurs coincident with E-selectin expression on endothelial cells within the target tissue and/or coincident with accumulation of leukocytes within the target tissue, and wherein said population exhibits enhanced localization and/or colonization within the inflamed and/or damaged tissue relative to a native population of the administered cells.

3 .- 7 . (canceled)

8 . A method of treating a tumor/malignant disease in a subject, the method comprising:
administering to the subject a population of cells that express an E-selectin ligand and/or an L-selectin ligand, the population expressing the E-selectin ligand and/or L-selectin ligand at a level that exceeds the level of expression of a native population of the cells, wherein said administration occurs coincident with E-selectin expression on endothelial cells within tissue(s) harboring tumor/malignant cells and/or coincident with accumulation of leukocytes within the tissue(s) harboring tumor/malignant cells.

9 .- 10 . (canceled)

11 . The method of claim 1 , wherein said cell administration occurs coincident with E-selectin expression on endothelial cells and infiltrates of leukocytes bearing L-selectin within the target tissue.

12 .- 13 . (canceled)

14 . The method of claim 1 , wherein an immunomodulatory effect is achieved by colonization of cells within an/the inflamed and/or damaged tissue.

15 . The method of claim 1 , wherein a tissue reparative effect is achieved by colonization of administered cells within an/the inflamed and/or damaged tissue.

16 . The method of claim 1 , wherein an enhanced host defense/immune response effect is achieved by delivery and colonization of administered cells within an/the inflamed and/or damaged tissue.

17 . The method of claim 1 , wherein an anti-malignancy effect is achieved by colonization of administered cells within a/the tumor/malignant tissue site.

18 .- 25 . (canceled)

26 . The method of claim 1 , wherein the population of cells express an E-selectin ligand and an L-selectin ligand.

27 . The method of claim 1 wherein the E-selectin ligand and/or L-selectin ligand is selected from one or more of Hematopoietic Cell E-/L-selectin Ligand (HCELL), Neural Cell Adhesion Molecule E-selectin Ligand (NCAM-E), CD43E, CLA, and ESL-1.

28 . The method of claim 1 , wherein the E-selectin ligand is Hematopoietic Cell E-/L-selectin Ligand (HCELL) and/or Neural Cell Adhesion Molecule E-selectin Ligand (NCAM-E).

29 . The method of claim 1 , wherein the E-selectin ligand is HCELL.

30 . The method of claim 1 , wherein the E-selectin ligand is NCAM-E.

31 . The method of claim 1 , wherein the L-selectin ligand is HCELL.

32 . The method of claim 1 , wherein the cell population comprises one or more of epithelial, endothelial, neuronal, adipose, cardiac, skeletal muscle, fibroblast, and immune cells (for example, dendritic cells, monocytes, macrophages, leukocytes (e.g., a lymphocyte such as a NK cell, a B-lymphocyte, a T-lymphocyte, or a subset of T-lymphocytes, such as regulatory lymphocyte (CD4 + /CD25 + /FOXP3 + )), a cytotoxic lymphocyte, etc.), hepatic, splenic, lung, circulating blood cells, platelets, reproductive cells, gastrointestinal, renal, bone marrow, pancreatic cells, a stem cell (e.g., a mesenchymal stem cell, a hematopoietic stem cell, a tissue stem/progenitor cell (for example, a neural stem cell, myocyte stem cell or pulmonary stem cell), an umbilical cord stem cell, or an embryonic stem cell, or an induced pluripotent stem cell, or a differentiated progenitor derived from an embryonic stem cell or from an induced pluripotent stem cells, or a differentiated progenitor derived from an adult stem cell, or a primary cell isolated from any tissue (e.g., brain, liver, lung, gut, stomach, fat, muscle, testes, uterus, ovary, skin, spleen, endocrine organ and bone), or a culture-expanded progenitor cell population, or a culture-expanded stem cell population, or a culture-expanded primary cell population.

33 .- 34 . (canceled)

35 . The method of claim 1 , wherein the disease, disorder or medical condition is one or more of direct tissue injury (e.g., burns, trauma, decubitus ulcers, etc.), ischemic/vascular events (e.g., myocardial infarct, stroke, shock, hemorrhage, coagulopathy, etc.), infections (e.g., cellulitis, pneumonia, meningitis, sepsis, SIRS, etc.), neoplasia (e.g., breast cancer, lung cancer, prostate cancer, lymphoma, leukemia, etc.), immunologic/autoimmune conditions (e.g., graft vs. host disease, multiple sclerosis, diabetes, inflammatory bowel disease, lupus erythematosus, rheumatoid arthritis, psoriasis, etc.), degenerative diseases (e.g., osteoporosis, osteoarthritis, Alzheimer's disease, etc.), congenital/genetic diseases (e.g., epidermolysis bullosa, osteogenesis imperfecta, muscular dystrophies, lysosomal storage diseases, Huntington's disease, etc.), adverse drug effects (e.g., drug-induced hepatitis, drug-induced cardiac injury, etc.), toxic injuries (e.g., radiation exposure(s), chemical exposure(s), alcoholic hepatitis, alcoholic pancreatitis, alcoholic cardiomyopathy, cocaine cardiomyopathy, etc.), metabolic derangements (e.g., uremic pericarditis, metabolic acidosis, etc.), iatrogenic conditions (e.g., radiation-induced tissue injury, surgery-related complications, etc.), and/or idiopathic processes (e.g., amyotrophic lateral sclerosis, Parsonnage-Turner Syndrome, etc.).

36 . The method of claim 1 , wherein the disease, disorder or medical condition is diabetes.

37 . The method of claim 1 , wherein the disease, disorder or medical condition is multiple sclerosis.

38 . The method of claim 1 , wherein the subject is a human, non-human primate, mouse, rat, dog, cat, horse, or cow.

39 . The method of claim 1 , wherein the subject is a human patient.

40 .- 53 . (canceled)

Assignees

• Brigham & Womens Hospital

Inventors

• Sackstein Robert

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title