Antibodies to CD70
The present invention relates to antibodies and antigen binding fragments thereof which bind to the human CD70 protein with high affinity and display potent inhibition of tumor cell growth.
1. A monoclonal antibody, or a fragment thereof, which specifically binds to an epitope of human CD70, wherein the epitope is within the amino acid sequence HIQVTLAICSS (SEQ ID NO:342), and which, when tested as a Fab fragment, has an off-rate (k off ) as measured by surface plasmon resonance for human CD70 of less than 7×10 −4 s −1 .
2. The monoclonal antibody or fragment thereof according to claim 1 , which, when tested as a Fab fragment, has an off-rate (k off ) as measured by surface plasmon resonance for human CD70 of less than or equal to 4.8×10 −4 s −1 .
3. The monoclonal antibody or fragment thereof according to claim 1 , which is a chimeric antibody or a humanized antibody.
4. The monoclonal antibody or fragment thereof according to claim 1 , which is a chimeric antibody, wherein the chimeric antibody comprises a constant domain derived from a human immunoglobulin.
5. The chimeric antibody according to claim 4 , wherein the constant domain is derived from a human immunoglobulin selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.
6. The chimeric antibody according to claim 4 , wherein the constant domain is derived from human IgG1.
7. The monoclonal antibody or fragment thereof according to claim 1 , wherein the monoclonal antibody or fragment thereof comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH and VL domains, or one or more complementarity-determining regions (CDRs) thereof, are derived from a camelid species.
8. The monoclonal antibody or fragment thereof claim 1 , wherein the monoclonal antibody or fragment thereof is a llama-human chimeric antibody comprising VH and VL domains, or one or more CDRs thereof, derived from llama, and one or more constant domains derived from a human immunoglobulin.
9. The monoclonal antibody or fragment thereof according to claim 1 , which is capable of directing immune effector function against a cell expressing human CD70 on its surface, wherein the immune effector function is selected from the group consisting of antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cellular phagocytosis (ADCP), and any combination thereof.
10. The monoclonal antibody or fragment thereof according to claim 1 , wherein the antibody fragment is an scFv, a F(ab′) 2 fragment, a Fab fragment, a Fab′ fragment, an Fd fragment, an Fv fragment, or a single domain antibody (Dab) fragment.
11. A pharmaceutical composition comprising the monoclonal antibody or fragment thereof according to claim 1 and a pharmaceutically acceptable carrier or excipient.
12. An immunoconjugate comprising the monoclonal antibody or fragment thereof according to claim 1 and a cytotoxic agent.
13. The immunoconjugate according to claim 12 , wherein the cytotoxic agent is selected from the group consisting of chemotherapeutic agents, toxins of bacterial, fungal, plant or animal origin, and radioactive isotopes.