Molecules that bind to CD66e polypeptides
This document provides methods and materials involved in binding a binder (e.g., an antibody, antigen binding fragment, antibody domain, CAR, cell engager, and/or ADC) to a CD66e polypeptide. For example, binders (e.g., antibodies, antigen binding fragments, antibody domains, CARs, cell engagers, and/or ADCs) that bind to a CD66e polypeptide and methods and materials for using one or more such binding molecules to treat a mammal (e.g., a human) having cancer are provided.
1 . An antibody or antigen binding fragment thereof comprising:
(i) a heavy chain variable domain (VH) and alight chain variable domain (VL), wherein said VH comprises a VH-CDR1 sequence of SEQ ID NO:1, a VH-CDR2 sequence of SEQ ID NO: 2, and a VH-CDR3 sequence of SEQ ID NO: 3, and said VL comprises a VL-CDR1 sequence of SEQ ID NO: 9, a VL-CDR2 sequence of SEQ ID NO: 10, and a VL-CDR3 sequence of SEQ ID NO: 11; or
(ii) a heavy chain variable domain (VH) and alight chain variable domain (VL), wherein said VH comprises a VH-CDR1 sequence of SEQ ID NO: 17, a VH-CDR2 sequence of SEQ ID NO: 18, and a VH-CDR3 sequence of SEQ ID NO: 19, and said VL comprises a VL-CDR1 sequence of SEQ ID NO: 25, a VL-CDR2 sequence of SEQ ID NO: 26, and a VL-CDR3 sequence of SEQ ID NO: 27;
wherein said antibody or antigen binding fragment thereof binds CD66e.
2 . The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding domain thereof comprises the ability to bind to SEQ ID NO:150 or SEQ ID NO:151.
3 . A chimeric antigen receptor comprising an antigen binding domain, a hinge, a transmembrane domain, and one or more signaling domains, wherein said antigen binding domain comprises the antibody or antigen binding fragment thereof of claim 1 .
4 . The chimeric antigen receptor of claim 3 , wherein said antigen binding domain is an scFv.
5 . A cell comprising the chimeric antigen receptor of claim 3 .
6 . The cell of claim 5 , wherein said cell is a T cell, a stem cell, or an NK cell.
7 . A cell engager comprising a first antigen binding domain, a linker, and a second antigen binding domain, wherein said first antigen binding domain comprises the antibody or antigen binding fragment thereof of claim 1 .
8 . The cell engager of claim 7 , wherein said first antigen binding domain is an scFv.
9 . The cell engager of claim 7 , wherein said first antigen binding domain is an IgG.
10 . The cell engager of claim 7 , wherein said second antigen binding domain binds to a polypeptide expressed on the surface of T cells.
11 . The cell engager of claim 10 , wherein said polypeptide expressed on the surface of T cells is a CD3 polypeptide.
12 . The cell engager of claim 7 , wherein said second antigen binding domain binds to a polypeptide expressed on the surface of NK cells.
13 . The cell engager of claim 12 , wherein said polypeptide expressed on the surface of NK cells is a CD16a, NKG2A, NKG2D, NKp30, NKp44, or NKp46 polypeptide.
14 . An antibody-drug conjugate (ADC) comprising an antigen binding domain covalently linked to a drug, wherein said antigen binding domain comprises the antibody or antigen binding fragment thereof of claim 1 .
15 . A method of treating a mammal having cancer, wherein said method comprises administering, to said mammal, a composition comprising (a) an antibody comprising (i) or (ii), (b) an antigen binding fragment comprising said (i) or said (ii), (c) a cell expressing a chimeric antigen receptor comprising an antigen binding domain comprising said (i) or said (ii), a hinge, a transmembrane domain, and one or more signaling domains, (d) a cell engager comprising a first antigen binding domain comprising said (i) or said (ii), a linker, and a second antigen binding domain, or (e) an ADC comprising a drug covalently linked to an antigen binding domain comprising said (i) or said (ii), wherein said
(i) is a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein said VH comprises a VH-CDR1 sequence of SEQ ID NO: 1, a VH-CDR2 sequence of SEQ ID NO: 2, and a VH-CDR3 sequence of SEQ ID NO: 3, and said VL comprises a VL-CDR1 sequence of SEQ ID NO: 9, a VL-CDR2 sequence of SEQ ID NO: 10, and a VL-CDR3 sequence of SEQ ID NO: 11, and wherein said
(ii) is a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein said VH comprises a VH-CDR1 sequence of SEQ ID NO: 17, a VH-CDR2 sequence of SEQ ID NO: 18, and a VH-CDR3 sequence of SEQ ID NO: 19, and said VL comprises a VL-CDR1 sequence of SEQ ID NO: 25, a VL-CDR2 sequence of SEQ ID NO: 26, and a VL-CDR3 sequence of SEQ ID NO: 27;
wherein said antibody, antigen binding fragment, cell, cell engager, or ADC binds CD66e.
16 . A method for binding a binding molecule to a CD66e polypeptide, wherein said method comprises contacting said CD66e polypeptide with the antibody or antigen binding fragment thereof of claim 1 .
17 . A method for binding a binding molecule to a CD66e polypeptide, wherein said method comprises contacting said CD66e polypeptide with (a) a chimeric antigen receptor comprising an antigen binding domain comprising (i) or (ii), a hinge, a transmembrane domain, and one or more signaling domains, (b) a cell engager comprising a first antigen binding domain comprising said (i) or said (ii), a linker, and a second antigen binding domain, or (c) an ADC comprising a drug covalently linked to an antigen binding domain comprising said (i) or said (ii), wherein said
(i) is a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein said VH comprises a VH-CDR1 sequence of SEQ ID NO: 1, a VH-CDR2 sequence of SEQ ID NO: 2, and a VH-CDR3 sequence of SEQ ID NO: 3, and said VL comprises a VL-CDR1 sequence of SEQ ID NO: 9, a VL-CDR2 sequence of SEQ ID NO: 10, and a VL-CDR3 sequence of SEQ ID NO: 11, and wherein said
(ii) is a heavy chain variable domain (VH) and a light chain variable domain (VL), wherein said VH comprises a VH-CDR1 sequence of SEQ ID NO: 17, a VH-CDR2 sequence of SEQ ID NO: 18, and a VH-CDR3 sequence of SEQ ID NO: 19, and said VL comprises a VL-CDR1 sequence of SEQ ID NO: 25, a VL-CDR2 sequence of SEQ ID NO: 26, and a VL-CDR3 sequence of SEQ ID NO: 27;
wherein said chimeric antigen receptor, cell engager, or ADC binds CD66e.