Cancer-killing cells
AssigneeLIfT BioSciences Ltd
InventorsAlex Blyth, Nico Bruyniks
Life of this patent
Estimating the term…
Abstract
The present invention relates to an in vitro culture of haematopoietic cells, wherein said haematopoietic cells differentiate to form granulocytes characterised by the ability to kill cancer cells. The invention also relates to said granulocytes, methods for identifying said haematopoietic cells and granulocytes, compositions and kits comprising the same, as well as uses of the same for treating cancer.
Claims57
An in vitro cell culture of haematopoietic cells, wherein said haematopoietic cells differentiate to form granulocytes characterised by:
- a. a surface potential defined by an electrophoretic mobility of at least 1.0 μm·cm/volt·sec;
- and
- b. the ability to kill cancer cells.
An in vitro cell culture of haematopoietic cells, wherein said haematopoietic cells differentiate to form granulocytes characterised by:
- a. a density of at least 1.077 g/ml;
- and
- b. the ability to kill cancer cells.
An in vitro cell culture of haematopoietic cells, wherein said haematopoietic cells differentiate to form granulocytes characterised by:
- a. expression or activity of toll-like receptors;
- and/or an absence of expression or inactivity of:
- programmed death 1 (PD-1) receptor;
- CD115;
- CD224;
- CXCR1;
- and/or CXCR2;
- and
- b. the ability to kill cancer cells.
An in vitro cell culture according to any one of the preceding claims, wherein the cell culture is enriched for the haematopoietic cells.
An in vitro cell culture according to any one of the preceding claims, wherein at least 70% of the cells in the in vitro cell culture are the haematopoietic cells.
An in vitro cell culture according to any one of the preceding claims, wherein the haematopoietic cells are obtainable from a donor, preferably a human donor.
An in vitro cell culture according to any one of the preceding claims, wherein the haematopoietic cells have a surface potential defined by an electrophoretic mobility of at least 1.0 μm·cm/volt·sec or at least 2.0 μm·cm/volt·sec or at least 2.5 μm·cm/volt·sec or at least 3.0 μm·cm/volt·sec.
An in vitro cell culture according to any one of the preceding claims, wherein the granulocytes have a surface potential defined by an electrophoretic mobility of at least 2.0 μm·cm/volt·sec or at least 2.5 μm·cm/volt·sec or at least 3.0 μm·cm/volt·sec.
An in vitro cell culture according to any one of the preceding claims, wherein the granulocyte is a neutrophil.
A method for selecting a haematopoietic cell suitable for use in treating cancer, said method comprising:
- a. measuring a surface potential of a granulocyte cell obtainable from a donor;
- and
- b. selecting a haematopoietic cell from said donor when the measured surface potential is defined by an electrophoretic mobility of at least 1.0 μm·cm/volt·sec.
A method for selecting a haematopoietic cell suitable for use in treating cancer, said method comprising:
- a. measuring the density of a granulocyte cell obtainable from a donor;
- and
- b. selecting a haematopoietic cell from said donor when the measured density of the granulocyte is at least 1.077 g/ml.
A method for selecting a haematopoietic cell suitable for use in treating cancer, said method comprising:
- a. detecting the expression or activity of toll-like receptors;
- programmed death 1 (PD-1) receptor;
- CD115;
- CD224;
- CXCR1;
- and/or CXCR2 on a granulocyte cell obtainable from a donor;
- and
- b. selecting a haematopoietic cell from said donor when the toll-like receptors are expressed or active;
- and/or programmed death 1 (PD-1) receptor;
- CD115;
- CD224;
- CXCR1;
- and/or CXCR2 are not expressed or are inactive.
A method for selecting a haematopoietic cell suitable for use in treating cancer, said method comprising:
- a. measuring a surface potential of the haematopoietic cell;
- and
- b. selecting a haematopoietic cell that has a greater surface potential than an otherwise identical haematopoietic cell that differentiates to form a granulocyte having a surface potential defined by an electrophoretic mobility of less than 1.0 μm·cm/volt·sec and/or has a reduced ability to kill cancer cells.
A method for selecting a haematopoietic cell suitable for use in treating cancer, said method comprising:
- a. measuring the density of a haematopoietic cell;
- and
- b. selecting a haematopoietic cell that has a density greater than an otherwise identical haematopoietic cell that differentiates to form a granulocyte having a density of less than 1.077 g/ml and/or has a reduced ability to kill cancer cells
An in vitro method for selecting a haematopoietic cell suitable for use in treating cancer, said method comprising:
- a. admixing a granulocyte obtainable from a donor with a cell line to form an admixture;
- b. incubating said admixture;
- c. measuring the % of cancer cells killed in said admixture;
- and
- d. selecting a haematopoietic cell from said donor when said granulocyte kills at least 70% of the cancer cells in the admixture.
Use of a surface potential of a haematopoietic cell, for selecting a cell that can be differentiated into a granulocyte that is suitable for treating cancer, wherein the surface potential is greater than the surface potential of an otherwise identical haematopoietic cell that differentiates to form a granulocyte having a surface potential defined by an electrophoretic mobility of less than 1.0 μm·cm/volt·sec and/or has a reduced ability to kill cancer cells.
An in vitro method for selecting a granulocyte suitable for use in treating pancreatic cancer, said method comprising:
- a. admixing a granulocyte with a pancreatic cancer cell line to form an admixture;
- b. incubating said admixture;
- c. measuring the % of pancreatic cancer cells killed in said admixture;
- and
- d. selecting a granulocyte that kills at least 70% of the pancreatic cancer cells in the admixture.
An in vitro method for selecting a granulocyte suitable for use in treating cancer, said method comprising:
- a. admixing a granulocyte with a plurality of different cancer cell lines to provide a plurality of admixtures;
- b. incubating said admixtures;
- c. measuring the % of cancer cells killed in said admixtures;
- and
- d. selecting a granulocyte as suitable for use in treating a cancer of the same type/subset as the cancer cell line, when said granulocyte kills at least 70% of the cancer cells in the admixture.
A pharmaceutical composition comprising:
- a. a haematopoietic cell or a granulocyte;
- and
- b. a granulocyte-macrophage colony-stimulating factor (GM-CSF), a granulocyte colony-stimulating factor (G-CSF), a growth hormone;
- serotonin, vitamin C, vitamin D, glutamine (Gln), arachidonic acid, AGE-albumin, an interleukin, TNF-alpha, Flt-3 ligand, thrombopoietin, foetal bovine serum (FBS), or combinations thereof.
Dependencies are inferred from the claim text.