Anti-GITR antibodies
Antibodies to human GITR are provided, as well as uses thereof, e.g., in treatment of proliferative and immune disorders.
1. An isolated antibody or antigen-binding fragment thereof that specifically binds to human GITR protein comprising:
a light chain immunoglobulin variable region that comprises CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 105, wherein residue 31 is Q and residue 57 is Q;
and
a heavy chain immunoglobulin variable region that comprises CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 104.
2. The antibody or antigen-binding fragment of claim 1 which is a humanized antibody comprising a human heavy chain constant region and a human light chain constant region.
3. A method of producing a humanized antibody that specifically binds to human GITR protein, comprising:
a humanized light chain immunoglobulin variable region that comprises CDR-L1, CDR-L2 and CDR-L3 of a light chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 105, wherein residue 31 is Q and residue 57 is Q,
and
a humanized heavy chain immunoglobulin variable region that comprises CDR-H1, CDR-H2 and CDR-H3 of a heavy chain immunoglobulin variable region comprising the amino acid sequence of SEQ ID NO: 104;
the method comprising:
culturing a Chinese hamster ovary host cell, that comprises a nucleic acid encoding the humanized light chain immunoglobulin operably linked to a promoter and a nucleic acid encoding the heavy chain immunoglobulin operably linked to a promoter, in culture medium under conditions wherein the humanized light chain immunoglobulin and the humanized heavy chain immunoglobulin are expressed; and recovering the humanized antibody from the host cell or culture medium or both.
4. The humanized antibody of claim 2 , comprising a γ1 human heavy chain constant region.
5. The humanized antibody of claim 2 , comprising a γ4 human heavy chain constant region.
6. The antibody or antigen-binding fragment of claim 1 , which is an antigen-binding fragment selected from the group consisting of Fab, Fab′, Fv, scFv, F(ab′) 2 , and a diabody.
7. A pharmaceutical composition comprising the humanized antibody of claim 2 and a pharmaceutically acceptable carrier.
8. The antibody or fragment of claim 1 which is an antibody.
9. The humanized antibody of claim 4 which comprises a kappa human light chain constant region.
10. The humanized antibody of claim 5 which comprises a kappa human light chain constant region.
11. The method of claim 3 wherein the humanized antibody comprises a γ4 human heavy chain constant region and a kappa human light chain constant region.
12. The method of claim 3 wherein the humanized antibody comprises a γ1 human heavy chain constant region and a kappa human light chain constant region.
13. The pharmaceutical composition of claim 7 wherein the humanized antibody comprises a γ1 human heavy chain constant region and a kappa human light chain constant region.
14. The pharmaceutical composition of claim 7 wherein the humanized antibody comprises a γ4 human heavy chain constant region and a kappa human light chain constant region.