Modified T lymphocytes comprising an inducible caspase and methods of apoptosis
AssigneeCelgene Corporation
InventorsStewart Abbot, Tianjian Li, Bitao Liang
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Abstract
Provided herein are cells, e.g., T cells expressing artificial cell death polypeptides that cause death of a cell, e.g., cells (e.g., T lymphocytes) expressing the cell death polypeptide, when the cell death polypeptide is multimerized or dimerized. Also provided herein is use of such cells, e.g., T lymphocytes, to treat diseases such as cancer.
Claims12
A T lymphocyte comprising an artificial cell death polypeptide comprising an apoptosis-inducing domain, wherein said artificial cell death polypeptide is a transmembrane protein comprising an extracellular domain that comprises a CD20 epitope, a transmembrane domain, and an intracellular domain comprising said apoptosis-inducing domain, wherein said apoptosis-inducing domain is caspase 3, caspase 8 or caspase 9, wherein said polypeptide is dimerizable using an anti-CD20 antibody that binds to said CD20 epitope, and wherein when said antibody dimerizes said polypeptide, an apoptosis-inducing signal is generated in said T lymphocyte.
A method of killing a T lymphocyte, wherein said T lymphocyte comprises a plurality of artificial cell death polypeptides each comprising an apoptosis-inducing domain, wherein said artificial cell death polypeptide is a transmembrane protein comprising an extracellular domain that comprises a CD20 epitope, a transmembrane domain, and an intracellular domain comprising said apoptosis-inducing domain, wherein said apoptosis-inducing domain is caspase 3, caspase 8 or caspase 9, wherein said polypeptide is dimerizable using an anti-CD20 antibody that binds to said CD20 epitope, and wherein when said antibody dimerizes said polypeptides, an apoptosis-inducing signal is generated in said T lymphocyte,
- comprising contacting said T lymphocyte with an amount of said antibody sufficient for said plurality of artificial cell death polypeptides to dimerize and generate an aggregate apoptosis-inducing signal sufficient to kill said T lymphocyte.
Dependencies are inferred from the claim text.