Antigen binding constructs to CD8
Antigen binding constructs that bind to CD8, for example antibodies, including antibody fragments (such as scFv, minibodies, and cys-diabodies) that bind to CD8, are described herein. Methods of use are described herein.
1. A antigen binding construct that comprises:
a variable heavy (V H ) domain comprising:
a HCDR1 of a HCDR1 of SEQ ID NO: 3 or 6;
a HCDR2 of HCDR2 of SEQ ID NO: 3 or 6;
a HCDR3 of HCDR3 of SEQ ID NO: 3 or 6;
a HFR3 of a HFR3 of SEQ ID NO: 48; and
a variable light (V L ) domain comprising:
a LCDR1 of LCDR1 of SEQ ID NO: 9;
a LCDR2 of LCDR2 of SEQ ID NO: 9; and
a LCDR3 of LCDR3 of SEQ ID NO: 9.
2. The antigen binding construct of claim 1 , wherein the antigen binding construct binds specifically to CD8.
3. The antigen binding construct of claim 1 , further comprising a detectable marker.
4. The antigen binding construct of claim 1 , further comprising a therapeutic agent.
5. The antigen binding construct of claim 1 , wherein the antigen binding construct is bispecific.
6. The antigen binding construct of claim 1 , wherein the antigen binding construct is a monovalent scFv.
7. A cys-diabody that binds to CD8, the cys-diabody comprising a polypeptide that comprises:
a single-chain variable fragment (scFv) comprising a variable heavy (V H ) domain linked to a variable light (V L ) domain; and
the V H domain comprising:
a HCDR1 of a HCDR1 of SEQ ID NO: 3 or 6;
a HCDR2 of a HCDR2 of SEQ ID NO: 3 or 6;
a HCDR3 of a HCDR3 of SEQ ID NO: 3 or 6; and
a HFR3 of a HFR3 of SEQ ID NO: 48; and
the V L domain comprising:
a LCDR1 of LCDR1 of SEQ ID NO: 9;
a LCDR2 of a LCDR2 of SEQ ID NO: 9; and
a LCDR3 of a LCDR3 of SEQ ID NO: 9.
8. The cys-diabody of claim 7 , wherein the order of the variable domains, from N terminus to C terminus of the polypeptide is V L , V H .
9. The cys-diabody of claim 7 , wherein the order of the variable domains, from N terminus to C terminus of the polypeptide is V H , V L .
10. The cys-diabody of claim 7 , further comprising a detectable molecule.
11. A minibody that binds to CD8, the minibody comprising a polypeptide that comprises from N-terminus to C-terminus:
a single-chain variable fragment (scFv) that binds to CD8, the scFv comprising a variable heavy (V H ) domain linked to a variable light (V L ) domain,
the V H domain comprising:
a HCDR1 of SEQ ID NO: 48;
a HCDR2 of SEQ ID NO: 48;
a HCDR3 of SEQ ID NO: 48;
a HFR3 of a HFR3 of SEQ ID NO: 48; and
the V L domain comprising:
a LCDR1 of SEQ ID NO: 42;
a LCDR2 of SEQ ID NO: 42; and
a LCDR3 of SEQ ID NO: 42;
a hinge-extension domain comprising a IgG1 hinge region; and
a IgG C H 3 sequence.
12. The minibody of claim 11 , further comprising a detectable marker.
13. A kit comprising:
an antigen binding construct of claim 1 ; and
a detectable marker.
14. The cys-diabody of claim 7 , further comprising:
a therapeutic agent; and
a cysteine tail comprising a disulfide linkage with the therapeutic agent.
15. The minibody of claim 11 , wherein the V H domain is a V H domain of SEQ ID NO: 48, and wherein the V L domain is a V L domain of SEQ ID NO: 42.
16. The minibody of claim 11 , wherein the minibody is humanized.
17. The antigen binding construct of claim 1 , wherein the antigen binding construct is humanized.
18. The antigen binding construct of claim 1 , wherein the V H domain is a V H domain of SEQ ID NO: 48, and wherein the V L domain is a V L domain of SEQ ID NO: 42.
19. The antigen binding construct of claim 1 , wherein the antigen binding construct is an antibody.
20. The antigen binding construct of claim 1 , wherein the variable heavy (V H ) domain comprises:
the amino acid sequence of positions 26-31 of SEQ ID NO: 48;
the amino acid sequence of positions 50-58 of SEQ ID NO: 48;
the amino acid sequence of positions 99-107 of SEQ ID NO: 48; and
the amino acid sequence of positions 59-98 of SEQ ID NO: 48; and
the variable light (V L ) domain comprises:
the amino acid sequence of positions 24-34 of SEQ ID NO: 42;
the amino acid sequence of positions 50-56 of SEQ ID NO: 42; and
the amino acid sequence of positions 89-97 of SEQ ID NO: 42.