CPC G01N 33/57492 (2013.01) [C12Q 1/6886 (2013.01); G16H 50/30 (2018.01); A61K 2039/515 (2013.01); C12Q 1/686 (2013.01)] | 10 Claims |
1. 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.
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