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. A method for investigating T-cell clonality of a T-cell malignancy in a subject which comprises the step of 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.
2. A method according to claim 1 which comprises the step of investigating TRBC2 expression in a tissue sample from the subject.
3. A method according to claim 2 wherein the sample is a formalin-fixed paraffin-embedded (FFPE) tissue sample.
4. A method according to claim 1 in which TRBC2 expression is investigated using immunohistochemistry.
5. 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) administering a TRBC2-specific therapeutic agent to a subject having a TRBC2-expressing T-cell malignancy, wherein the TRBC2-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.
6. A method according to claim 1 , wherein the T-cell malignancy is a T cell lymphoma or leukemia.
7. A method according to claim 6 , 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).
8. A method according to claim 5 , wherein the T-cell malignancy is a T cell lymphoma or leukemia.
9. A method according to claim 8 , 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).
10. A polyclonal antibody preparation which binds T-cell receptor constant region 2 (TRBC2) intracellular portion having the sequence shown as SEQ ID NO: 1 (VKRKDSRG) and does not cross-react with T-cell receptor constant region 1 (TRBC1).
11. A polyclonal antibody preparation according to claim 10 , which was obtained by a method which comprises the following steps:
(i) immunisation of an animal with a peptide comprising the sequence VKRKDSRG (SEQ ID NO: 1);
(ii) isolation of antibodies from the serum of the immunised animal to give a polyclonal antibody preparation; and
(iii) depletion of any TRBC1-reactive antibodies using a peptide comprising the sequence VKRKDF (SEQ ID NO: 2).