Cd4 + and cd8 + single positive t cells and compositions and methods for generating the same
AssigneeClade Therpaeutics, Inc.
InventorsDar Mikael HEINZE, Gordon Grant WELSTEAD
Life of this patent
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Abstract
Provided herein are cell and matrix compositions for the production of single positive T cells, such as CD4+ single positive T cells or CD8+ single positive T cells. Various methods for the generation of T cells by differentiation of stem cells are also provided. Further provided herein are methods of treating a disease or a condition in a subject, including, but not limited to cancer and autoimmune diseases.
Claims59
A composition comprising:
- a matrix;
- a plurality of cell surface receptor binding agents, wherein the plurality of cell surface receptor binding agents are bound to the matrix and comprise:
- a CD4 receptor binding agent;
- a T cell receptor (TCR) binding agent;
- and
- a population of single positive CD4 T cells (CD4+ CD8−).
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A composition comprising:
- a matrix;
- a plurality of cell surface receptor binding agents, wherein the plurality of cell surface receptor binding agents are bound to the matrix and comprise:
- a CD4 receptor binding agent;
- and
- a T cell receptor (TCR) binding agent;
- and
- a mixed population of in vitro-differentiated T cells, wherein the mixed population of in vitro-differentiated T cells comprise:
- a population of single positive CD4+ T cells;
- and
- a population of double positive (CD4+ CD8+) T cells,
- wherein the population of single positive CD4+ T cells is at least about 10% of a total number of cells within the mixed population of in vitro-differentiated T cells.
-85. (canceled)
A method of producing a population of single positive CD4+ T cells from a population of in vitro-differentiated double positive (CD4+ CD8+) T cells, the method comprising:
- contacting a population of in vitro-differentiated (CD4+ CD8+) T cells for a period of time with a composition comprising:
- (i) a matrix;
- (ii) a CD4 receptor binding agent that is bound to the matrix;
- and
- (iii) a TCR binding agent that is bound to the matrix,
- thereby producing a population of single positive CD4+ T cells.
-108. (canceled)
-113. (canceled)
A method for producing a single positive CD4+ T cell from a double positive (CD4+ CD8+) T cell, the method comprising:
- contacting an in vitro-differentiated double positive (CD4+ CD8+) T cell with a CD4 binding agent tethered to a TCR binding agent.
-123. (canceled)
A method for producing a single positive CD8+ T cell from a double positive (CD4+ CD8+) T cell, the method comprising:
- contacting an in vitro-differentiated double positive (CD4+ CD8+) T cell with a CD8 binding agent tethered to a TCR binding agent.
-131. (canceled)
A method of producing a population of single positive CD8+ T cells from a population of in vitro-differentiated double positive (CD4+ CD8+) T cells, the method comprising:
- contacting a population of in vitro-differentiated CD4+ CD8+ T cells for a period of time with a composition comprising:
- (i) a matrix;
- (ii) a CD8 binding agent that is bound to the matrix;
- and
- (iii) a TCR binding agent that is bound to the matrix,
- thereby producing a population of single positive CD8+ T cells.
-151. (canceled)
-174. (canceled)
A fusion protein comprising a CD4 binding agent that binds to SEQ ID NO:
- 1 or a functional fragment thereof;
- and a TCR binding agent that binds to SEQ ID NO:
- 2 or a functional fragment thereof.
A fusion protein comprising a CD8 binding agent that binds to SEQ ID NO:
- 3 or a T functional fragment thereof;
- and a TCR binding agent that binds to SEQ ID NO:
- 2 or a functional fragment thereof.
-189. (canceled)
A system for producing a single positive CD4+ T cell comprising:
- a cell culture vessel configured for localizing a plurality of cell surface receptor binding agents to an in vitro-differentiated double positive (CD4+ CD8+) T cell or a population thereof comprising;
- a matrix;
- a plurality of cell surface receptor binding agents, wherein the plurality of cell surface receptor binding agents are bound to the matrix and comprise:
- a CD4 receptor binding agent;
- a TCR binding agent;
- and
- an in vitro-differentiated double positive (CD4+ CD8+) T cell or a population thereof, wherein the plurality of cell surface receptor binding agents bind to the in vitro-differentiated double positive (CD4+ CD8+) T cell for a period of time,
- and wherein the cell culture vessel is configured to facilitate contact between the plurality of cell surface receptor binding agents and the in vitro-differentiated double positive CD4+ CD8+ T cell or population thereof, thereby producing a single positive CD4+ T cell within at least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, up to 20 days.
A system for producing a single positive CD8+ T cell comprising:
- a cell culture vessel configured localizing a plurality of cell surface receptor binding agents to an in vitro-differentiated double positive (CD4+ CD8+) T cell or a population thereof comprising;
- a matrix;
- a plurality of cell surface receptor binding agents, wherein the plurality of cell surface receptor binding agents are bound to the matrix and comprise:
- a CD8 receptor binding agent;
- a TCR binding agent;
- and
- an in vitro-differentiated double positive (CD4+ CD8+) T cell or a population thereof, wherein the plurality of cell surface receptor binding agents bind to the in vitro-differentiated double positive (CD4+ CD8+) T cell for a period of time,
- and wherein the cell culture vessel is configured to facilitate contact between the plurality of cell surface receptor binding agents and the in vitro-differentiated double positive CD4+ CD8+ T cell or population thereof, thereby producing a single positive CD8+ T cell within at least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, up to 20 days.
Dependencies are inferred from the claim text.