T-CELL RECEPTOR CONSTANT REGION 1 ANTIBODY OR T-CELL RECEPTOR CONSTANT REGION 2 ANTIBODY
The present invention provides antibodies and polyclonal antibody preparations which bind the intracellular portion of either T-cell receptor constant region 2 (TRBC2) or T-cell receptor constant region 1 (TRBC1). The antibodies can be used to determine whether a T-cell malignancy clonally expresses TRBC1 or TRBC2.
1 - 6 . (canceled)
7 . A method for investigating T-cell clonality of a T-cell malignancy in a subject which comprises detecting the expression of T-cell receptor constant region 1 (TRBC1) by malignant T cells from said subject using a polyclonal antibody which binds the TRBC1 intracellular portion having the sequence VKRKDF (SEQ ID NO: 2) and which does not cross-react with TRBC2 to establish whether malignant T cells from the subject express TRBC1.
8 . A method according to claim 7 , which comprises the step of investigating TRBC1 expression in a tissue sample from the subject.
9 . A method according to claim 8 , wherein the sample is a formalin-fixed paraffin-embedded (FFPE) tissue sample.
10 . A method according to claim 7 , in which TRBC1/TRBC2 expression is investigated using immunohistochemistry.
11 . A method for treating a T-cell malignancy in a subject, which comprises the following steps:
a) investigating the clonality of the T-cell malignancy malignancy comprising detecting the expression of TRBC1 by malignant T cells from said subject using a polyclonal antibody which binds the TRBC1 intracellular portion having the sequence VKRKDF (SEQ ID NO: 2) and which does not cross react with TRBC2 to establish whether malignant T cells from the subject express TRBC1 and
b) administering a TRBC1-specific therapeutic agent to a subject having a TRBC1-expressing T-cell malignancy,
wherein the TRBC1-specific therapeutic agent is a therapeutic antibody, an antibody-drug conjugate, a bispecific T-cell engager, or a chimeric antigen receptor (CAR)-T cell composition.
12 . (canceled)
13 . A method according to claim 7 , wherein the T-cell malignancy is a T cell lymphoma or leukemia.
14 . A method according to claim 13 , wherein the T cell lymphoma or leukemia is selected from: peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); angio-immunoblastic T-cell lymphoma (AITL); anaplastic large cell lymphoma (ALCL); enteropathy-associated T-cell lymphoma (EATL); hepatosplenic T-cell lymphoma (HSTL); extranodal NK/T-cell lymphoma nasal type; cutaneous T-cell lymphoma; primary cutaneous ALCL; T cell prolymphocytic leukaemia and T-cell acute lymphoblastic leukaemia (T-ALL).
15 . A method according to claim 11 , wherein the T-cell malignancy is a T cell lymphoma or leukemia.
16 . A method according to claim 15 , wherein the T cell lymphoma or leukemia is selected from: peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); angio-immunoblastic T-cell lymphoma (AITL); anaplastic large cell lymphoma (ALCL); enteropathy-associated T-cell lymphoma (EATL); hepatosplenic T-cell lymphoma (HSTL); extranodal NK/T-cell lymphoma nasal type; cutaneous T-cell lymphoma; primary cutaneous ALCL; T cell prolymphocytic leukaemia and T-cell acute lymphoblastic leukaemia (T-ALL).
17 . A method for treating a T-cell malignancy in a subject, which comprises the following steps:
a) investigating the clonality of the T-cell malignancy comprising detecting the expression of TRBC2 by malignant T cells from said subject using a polyclonal antibody which binds the T-cell receptor constant region 2 (TRBC2) intracellular portion having the sequence VKRKDSRG (SEQ ID NO: 1) and which does not cross-react with T-cell receptor constant region 1 (TRBC1), to establish whether malignant T cells from the subject express TRBC2; and
b) when expression of TRBC2 by the malignant cells from said subject is not detected, administering a TRBC1-specific therapeutic agent to the subject, wherein the TRBC1-specific therapeutic agent is a therapeutic antibody, an antibody-drug conjugate, a bispecific T-cell engager, or a chimeric antigen receptor (CAR)-T cell composition.
18 . A method according to claim 17 , wherein the T-cell malignancy is a T cell lymphoma or leukemia.
19 . A method according to claim 18 , wherein the T cell lymphoma or leukemia is selected from: peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); angio-immunoblastic T-cell lymphoma (AITL); anaplastic large cell lymphoma (ALCL); enteropathy-associated T-cell lymphoma (EATL); hepatosplenic T-cell lymphoma (HSTL); extranodal NK/T-cell lymphoma nasal type; cutaneous T-cell lymphoma; primary cutaneous ALCL; T cell prolymphocytic leukaemia and T-cell acute lymphoblastic leukaemia (T-ALL).