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US 11,885,807 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 TOR 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.
Claims8
A method of depleting malignant T-cells in a human subject with a TRBC2 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 TRBC2 positive T-cell lymphoma or leukaemia when the percentage of TRBC2 positive cells is greater than 80%, and
- selectively depleting T-cells in the subject determined to have the TRBC2 positive T cell lymphoma or leukaemia by administering an agent that selectively binds to and depletes malignant and normal T cells that are TRBC2-positive,
- wherein the agent is an engineered T-cell expressing a CAR which selectively binds TRBC2 and which comprises:
- (i) a spacer comprising an IgG1 hinge or a CD8 stalk, and (ii) an endodomain comprising a CD28 co-stimulatory component and a CD3-Zeta component.
3 more elements
A method of selectively depleting TRBC2 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 TRBC2, and
- selectively depleting malignant and normal T-cells in the subject that express TRBC2 by administering to the subject an agent that selectively binds to TRBC2 and that depletes said malignant and normal T-cells, wherein the agent is an engineered T-cell expressing a CAR that selectively binds to TRBC2 and that comprises:
- (i) a spacer comprising an IgG1 hinge or a CD8 stalk, and (ii) an endodomain comprising a CD28 co-stimulatory component and a CD3-Zeta component.
Dependencies are inferred from the claim text.