Anti-NKG2A antibodies and uses thereof
Described herein are anti-NKG2A antibodies suitable for human therapy, including humanized versions of murine anti-NKG2A antibody Z270, as well as related methods and materials for producing and using such antibodies. Exemplary complementarity-determining regions (CDRs) sequences and sites for optional amino acid back-substitutions in framework region (FR) and/or CDRs of such antibodies are also described.
1. An isolated antibody that specifically binds NKG2A, the antibody comprising antigen-binding residues from the complementarity-determining regions (CDRs) of murine antibody Z270 and human acceptor framework sequences, wherein said antibody comprises a VL domain that is at least 90% identical to SEQ ID NO: 4 and a VH domain that is at least 90% identical to SEQ ID NO:5, and wherein said antibody comprises CDR-H1 corresponding to residues 31-35 of SEQ ID NO: 5, CDR-H2 corresponding to residues 50-60 of SEQ ID NO: 5, CDR-H3 corresponding to residues 99-114 of SEQ ID NO: 5, CDR-L1 corresponding to residues 24-34 of SEQ ID NO: 4, CDR-L2 corresponding to residues 50-56 of SEQ ID NO: 4 and CDR-L3 corresponding to residues 89-97 of SEQ ID NO: 4.
2. The antibody of claim 1 , wherein:
the amino acid at position 5 of the VH domain is V or Q;
the amino acid at position 70 of the VH domain is M or L;
the amino acid at position 72 of the VH domain is T or V;
the amino acid at position 74 of the VH domain is T or K; or
the amino acid at position 76 of the VH domain is T or S.
3. The antibody of claim 1 , wherein the VII domain human acceptor framework sequences are free of any back-mutations.
4. The antibody of claim 1 , wherein the VH domain comprises the sequence of SEQ ID NO: 5.
5. The antibody of claim 4 , wherein the VL domain comprises SEQ ID NO: 4.
6. The antibody of claim 1 , which is an IgG4 antibody.
7. The antibody of claim 1 , which is an antibody fragment or a multispecific antibody.
8. A method for producing an anti-NKG2A antibody, comprising culturing a host cell comprising a nucleic acid encoding the anti-NKG2A antibody of claim 1 so that the nucleic acid is expressed and the antibody produced.
9. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.