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US 11,885,806 B2Granted
Method for depleting malignant T-cells
AssigneeAutolus Limited
InventorsMartin Pulé, Paul Maciocia
Life of this patent
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Abstract
The present invention relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.
Claims10
A method of depleting malignant T-cells in a human subject with a TRBC1 positive T-cell lymphoma or leukaemia, the method comprising:
- determining the percentage of total T-cells in a sample from the subject which is TRBC1 positive and determining the percentage of total T-cells in the sample which is TRBC2 positive,
- detecting a percentage of TRBC1 positive T-cells that is greater than 80% or detecting a percentage of TRBC2 positive T-cells that is greater than 80%,
- diagnosing the subject as having a TRBC1 positive T-cell lymphoma or leukaemia when the percentage of TRBC1 positive cells is greater than 80%, and
- selectively depleting T-cells in the subject determined to have the TRBC1 positive T cell lymphoma or leukaemia by administering an agent that selectively binds to and depletes malignant and normal T cells that are TRBC1-positive,
- wherein the agent is an engineered T-cell expressing a CAR which selectively binds TRBC1 and which comprises (a) an antigen-binding domain comprising a variable heavy chain (VH) comprising:
- a VH CDR1 of SEQ ID NO:
- 7, a VH CDR2 of SEQ ID NO:
- 8, and a VH CDR3 of SEQ ID NO:
- 9, and a variable light chain (VL) comprising a VL CDR1 of SEQ ID NO:
- 10, a VL CDR2 of SEQ ID NO:
- 11, and a VL CDR3 of SEQ ID NO:
- 12, and (b) a spacer comprising an IgG1 hinge or a CD8 stalk.
9 more elements
A method of selectively depleting TRBC1 positive malignant T-cells without depleting the entire T-cell compartment in a human subject, the method comprising:
- determining whether a malignant T cell in a sample containing T cells from the subject expresses TRBC1, and
- selectively depleting malignant and normal T-cells in the subject that express TRBC1 by administering to the subject an agent that selectively binds to TRBC1 and that depletes said malignant and normal T-cells,
- wherein the agent is an engineered T-cell expressing a CAR that selectively binds to TRBC1 and that comprises (a) an antigen-binding domain comprising a variable heavy chain (VH) comprising:
- a VH CDR1 of SEQ ID NO:
- 7, a VH CDR2 of SEQ ID NO:
- 8, and a VH CDR3 of SEQ ID NO:
- 9, and a variable light chain (VL) comprising a VL CDR1 of SEQ ID NO:
- 10, a VL CDR2 of SEQ ID NO:
- 11, and a VL CDR3 of SEQ ID NO:
- 12, and (b) comprises a spacer comprising an IgG1 hinge or a CD8 stalk.
7 more elements
Dependencies are inferred from the claim text.