Method

Abstract

The present invention relates to immunotherapeutic approaches to treating haematological cancers. In particular the invention relates to a method for treating a haematological cancer by targeting the 5T4 antigen. As such, the invention provides a method for treating haematological cancers comprising administering to a subject a 5T4-targeting agent. The invention also provides a 5T4-specific chimeric antigen receptor (CAR) and uses thereof in treating cancers.

1 . A method for treating a haematological cancer in a subject in need of treatment for said haematological cancer, the method comprising administering a 5T4-targeting agent to the subject, wherein said haematological cancer is not pre-B acute lymphoblastic leukaemia (B-ALL). 
     
     
         2 . The method according to  claim 1  wherein said 5T4-targeting agent is an antibody or a biologically active fragment thereof that binds 5T4. 
     
     
         3 . The method according to  claim 2   1  wherein said 5T4 targeting agent is a monoclonal antibody or a biologically active fragment thereof that binds 5T4. 
     
     
         4 . The method according to  claim 3  wherein said monoclonal antibody is based on an H8 5T4-specific antibody or a 2E4 5T4-specific antibody. 
     
     
         5 . The method according to  claim 4 , wherein said antibody is in the form of an antibody-drug conjugate. 
     
     
         6 . The method according to  claim 1  wherein said 5T4-targeting agent is an immune cell that recognizes 5T4. 
     
     
         7 . The method according to  claim 6  wherein said immune cell is a T cell, NK cell or NKT cell. 
     
     
         8 . The method according to  claim 7  wherein said immune cell is a T cell. 
     
     
         9 . The method according to  claim 6 , wherein said cell comprises a 5T4-specific chimeric antigen receptor (CAR) or T cell receptor (TCR). 
     
     
         10 . The method of  claim 1  wherein said 5T4-targeting agent is a 5T4 vaccine. 
     
     
         11 . The method according to  claim 1 , wherein said 5T4-targeting agent is administered via intravenous administration. 
     
     
         12 . The method according to  claim 1 , wherein said subject is a mammalian subject. 
     
     
         13 . The method according to  claim 1 , wherein said subject is a human subject. 
     
     
         14 . The method according to  claim 1 , wherein said haematological cancer is a leukaemia, a lymphoma, or a myeloma. 
     
     
         15 . The method according to  claim 14 , wherein said haematological cancer is selected from chronic lymphocytic leukaemia, myeloma, acute myeloid leukaemia, B cell acute lymphoblastic leukaemia, chronic myeloid leukaemia, and T cell acute lymphoblastic leukaemia. 
     
     
         16 . The method according to  claim 1 , wherein said 5T4-targeting agent is administered in combination with a further cancer therapy either simultaneously or sequentially. 
     
     
         17 - 18 . (canceled) 
     
     
         19 . The method of treating a haematological cancer in a subject according to  claim 1 , wherein said method comprises pre-screening a sample from the subject for 5T4 expression in the haematological cancer. 
     
     
         20 - 22 . (canceled) 
     
     
         23 . A 5T4-specific CAR comprising an extracellular ligand binding domain comprising VH and VL from a monoclonal anti-5T4 antibody, a hinge, a transmembrane domain and a cytoplasmic domain including a signalling domain and a co-stimulatory domain, wherein said CAR has the sequence set out in SEQ ID NO:_1 or a sequence with at least 92% sequence identity to SEQ ID NO:_1. 
     
     
         24 . A 5T4-specific CAR comprising an extracellular ligand binding domain comprising VH and VL from a monoclonal anti-5T4 antibody, a hinge, a transmembrane domain and a cytoplasmic domain including a signalling domain and a co-stimulatory domain, wherein said CAR has the sequence set out in SEQ ID NO:_13 or a sequence with at least 92% sequence identity to SEQ ID NO:_13. 
     
     
         25 . An immune cell comprising a 5T4-specific CAR according to  claim 23 . 
     
     
         26 . A population of immune cells according to  claim 25 . 
     
     
         27 . The immune cell according to  claim 25  wherein said cell is a T cell. 
     
     
         28 . The immune cell according to  claim 25  wherein said cell is an NK cell or an NKT cell. 
     
     
         29 . A composition comprising a population of cells according to  claim 26 . 
     
     
         30 . A method for treating cancer in a subject comprising administering to a subject in need thereof the 5T4-specific CAR according to  claim 23 , an immune cell comprising said 5T4-specific CAR, a population of said immune cells, or composition comprising a population of said immune cells. 
     
     
         31 - 33 . (canceled) 
     
     
         34 . The method according to  claim 30 , wherein said 5T4-specific CAR, cell, cell population, or composition administered intravenously, intraperitoneally or intraplurally. 
     
     
         35 . The method according to  claim 30 , wherein said cancer is myeloma or acute lymphoblastic leukaemia or chronic myeloid leukaemia. 
     
     
         36 . The method according to  claim 30 , wherein said cancer is ovarian cancer or mesothelioma. 
     
     
         37 . The method of treating myeloma in a subject according to  claim 30 , wherein said method comprises pre-screening the subject for 5T4 expression. 
     
     
         38 . (canceled) 
     
     
         39 . A method of making an immune cell expressing a 5T4-specific CAR according to  claim 23 , wherein said method comprises transducing said immune cell with a viral vector expressing said CAR. 
     
     
         40 . The method according to  claim 39 , wherein the viral vector is a lentiviral vector. 
     
     
         41 . The method according to  claim 40 , wherein the lentiviral vector is derived from HIV-1, HIV-2, SIV, FIV, BIV, EIAV, CAEV or visna lentivirus. 
     
     
         42 . A method for reducing cancer relapse in a subject, wherein said method comprises administering the 5T4-targeting agent according to  claim 1  to said subject. 
     
     
         43 . The method according to  claim 42  wherein said cancer is a haematological cancer or a cancer characterised by a solid tumour. 
     
     
         44 . The method according to  claim 43 , wherein said haematological cancer is chronic lymphocytic leukaemia, myeloma, acute myeloid leukaemia, or B cell acute lymphoblastic lymphoma. 
     
     
         45 . The method according to  claim 43 , wherein said cancer is ovarian cancer, glioblastoma, or colorectal cancer. 
     
     
         46 . The method according to  claim 30 , wherein said cancer comprises a solid tumour.