ALS Treatment Using Induced Regulatory T (iTREG) Cells
AssigneeRapa Therapeutics, LLC
InventorDaniel Harding FOWLER
Life of this patent
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Abstract
The present disclosure provides methods for treating ALS using pentostatin and cyclophosphamide treatment followed by TREG and/or TREG/Th2 hybrid cells from de-differentiated T cells. The present disclosure further provides methods for producing TREG and TREG/Th2 hybrid cells from de-differentiated T cells, said TREG and TREG/Th2 hybrid cells, populations thereof and compositions thereof. Methods for producing de-differentiated T cells, said de-differentiated T cells, populations thereof and compositions thereof are also provided.
Claims164
A method for treating amyotrophic lateral sclerosis in a subject in need thereof, comprising:
- subjecting said subject to one or more primary treatment cycles, each of said one or more primary treatment cycles comprising:
- administering to said subject pentostatin;
- and/or
- administering to said subject cyclophosphamide;
- and
- subjecting said subject to one or more immune therapy treatment cycles comprising:
- administering to said subject a composition comprising a therapeutically effective amount of manufactured TREG cells.
A method for the treatment of amyotrophic lateral sclerosis in a subject in need thereof, comprising:
- a first treatment cycle, a second treatment cycle, optionally, one or more additional treatment cycles, and one or more immune therapy treatment cycles,
- said first treatment cycle comprising:
- administering pentostatin to said subject, and/or
- administering cyclophosphamide to said subject;
- said second treatment cycle comprising:
- administering pentostatin to said subject, and/or
- administering cyclophosphamide to said subject;
- each of said one or more additional treatment cycles comprising:
- administering pentostatin to said subject, and/or
- administering cyclophosphamide to said subject
- each of said one or more immune therapy treatment cycles comprising:
- administering pentostatin to said subject, and/or
- administering cyclophosphamide to said subject, and
- administering manufactured TREG cells to said subject.
A method for treating amyotrophic lateral sclerosis in a subject in need thereof, comprising:
- one or more treatment cycles comprising:
- administering to said subject a therapeutically effective amount of manufactured TREG cells.
A method for treating amyotrophic lateral sclerosis in a subject in need thereof, comprising:
- administering to said subject a therapeutically effective amount of manufactured TREG cells.
A method for differentiating de-differentiated T cells to TREG/Th2 cells, comprising:
- culturing de-differentiated T cells in a culture medium comprising IL-2, IL-4 and TGF-β;
- adding anti-CD3/anti-CD28 coated magnetic beads at a ratio of 3:1 (bead:T cell ratio);
- incubating said de-differentiated T cells for a period of time to yield TREG/Th2 cells.
A method for differentiating de-differentiated T cells to TREG/Th2 cells, comprising:
- culturing de-differentiated T cells, wherein said de-differentiated T cells express RAPTOR and RICTOR at a level that is at least 10% reduced relative to control T cells in a culture medium comprising IL-2, IL-4 and TGF-β;
- adding anti-CD3/anti-CD28 coated magnetic beads at a ratio of 3:1 (bead:T cell ratio);
- incubating said de-differentiated T cells for a period of time to yield TREG/Th2 cells.
A method for differentiating de-differentiated T cells to TREG cells, comprising:
- culturing de-differentiated T cells having reduced expression of RAPTOR and RICTOR relative to a control population of T cells in a culture medium comprising IL-2 and TGF-β;
- adding anti-CD3/anti-CD28 coated magnetic beads at a ratio of 3:1 (bead:T cell ratio);
- incubating said de-differentiated T cells for a period of time to yield TREG cells.
A method for differentiating de-differentiated T cells to TREG cells, comprising:
- culturing de-differentiated T cells, wherein said de-differentiated T cells express RAPTOR and RICTOR at a level that is at least 10% reduced relative to control T cells in a culture medium comprising IL-2 and TGF-β;
- adding anti-CD3/anti-CD28 coated magnetic beads at a ratio of 3:1 (bead:T cell ratio);
- incubating said de-differentiated T cells for a period of time to yield TREG cells.
A population of TREG or TREG/Th2 cells having at least 5% of CD4+ or CD8+ T cells that express GATA3.
A population of TREG or TREG/Th2 cells having at least 5% of CD4+ or CD8+ T cells that express FoxP3
A population of TREG or TREG/Th2 cells having at least 10% of CD4+ or CD8+ T cells that express CD73.
A population of TREG or TREG/Th2 cells having at least 10% of CD4+ or CD8+ T cells that express CD103.
A population of TREG or TREG/Th2 cells having at least 20% of CD4+ or CD8+ T cells that express CD150.
A population of TREG or TREG/Th2 cells that expresses at least 5 pg/mL of IL-4 after co-stimulation with anti-CD3/anti-CD28 beads at a bead:T cell ratio of 3:1.
A population of TREG or TREG/Th2 cells that expresses at least 100 pg/mL of IL-2 after co-stimulation with anti-CD3/anti-CD28 beads at a bead:T cell ratio of 3:1.
A population of TREG or TREG/Th2 cells that expresses less than 100 μg/mL of IFN-γ or GM-CSF after co-stimulation with anti-CD3/anti-CD28 beads at a bead:T cell ratio of 3:1.
A population of TREG or TREG/Th2 cells that expresses less than 100 μg/mL of TNF-α or IL-17F after co-stimulation with anti-CD3/anti-CD28 beads at a bead:T cell ratio of 3:1.
Dependencies are inferred from the claim text.