Anti-CD70 antibody and its use for the treatment and prevention of cancer and immune disorders
View Patent ↗Disclosed are CD70 binding agents, such as anti-CD70 antibodies and derivatives, that induce a cytotoxic, cytostatic or immunomodulatory without conjugation to a therapeutic agents as well as pharmaceutical compositions and kits comprising the antibody or derivative. Also disclosed are methods for the treatment and prevention of CD70-expressing cancers and immunological disorders comprising administering the CD70 binding agents to a subject.
1. A method for the treatment of a CD70-expressing non-Hodgkin's lymphoma in a subject, comprising:
administering to the subject an effective amount of an antibody having an antigen-binding region that binds to CD70 and at least one effector domain mediating at least an ADCC, ADCP or CDC response in the subject, wherein the antibody exerts a cytostatic or cytotoxic effect in the absence of conjugation to a therapeutic agent and wherein the antibody is not conjugated to a therapeutic agent,
wherein the CD70-expressing non-Hodgkin's lymphoma is a mantle cell lymphoma.
2. The method of claim 1 , wherein the antibody is a chimeric, humanized, or fully human antibody.
3. The method of claim 2 , wherein the antibody is a humanized antibody.
4. The method of claim 3 , wherein the humanized antibody comprises an effector domain of a human IgM or IgG antibody.
5. The method of claim 4 , wherein the IgG antibody is of the human IgG1 subtype.
6. The method of claim 2 , wherein the antibody is a chimeric antibody.
7. The method of claim 6 , wherein the chimeric antibody comprises an effector domain of a human IgM or IgG antibody.
8. The method of claim 7 , wherein the IgG antibody is of the human IgG1 subtype.
9. The method of claim 2 , wherein the antibody comprises a human constant region.
10. The method of claim 1 , wherein the antibody comprises H1, H2, H3, L1, L2 and L3 complementarity-determining regions having, respectively, the amino acid sequences set forth in SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10; SEQ ID NO:16, SEQ ID NO:18, and SEQ ID NO:20.
11. The method of claim 1 , wherein the antibody comprises a heavy chain variable region having the amino acid sequence set forth in residues 20-137 of SEQ ID NO:2 or residues 20-137 of SEQ ID NO:22.
12. The method of claim 11 , wherein the antibody-further comprises a light chain variable region having the amino acid sequence set forth in residues 21-132 of SEQ ID NO:12 or residues 21-132 of SEQ ID NO:32.
13. The method of claim 1 , wherein the antibody comprises a light chain variable region having the amino acid sequence set forth in residues 21-132 of SEQ ID NO:12 or residues 21-132 of SEQ ID NO:32.
14. The method of claim 10 , wherein the antibody is a humanized antibody.
15. The method of claim 10 , wherein the antibody is a chimeric antibody.
16. The method of claim 1 , wherein the antibody is multivalent.
17. The method of claim 1 , further comprising administering a therapeutic agent.
18. The method of claim 17 , wherein the therapeutic agent is a cytostatic, cytotoxic or immunomodulatory agent.
19. The method of claim 18 , wherein the therapeutic agent is a cytostatic or cytotoxic agent.
20. The method of claim 1 , wherein the subject is human.
21. The method of claim 1 , wherein the antibody comprises H1, H2, and H3 complementarity determining regions having the amino acid sequences set forth in SEQ ID NO:26, SEQ ID NO:28 and SEQ ID NO:30, respectively, and further comprises L1, L2, and L3 complementarity determining regions having the amino acid sequences set forth in SEQ ID NO:36, SEQ ID NO:38 and SEQ ID NO:40, respectively.
22. The method of claim 1 , wherein the antibody competes for binding to CD70 with a second antibody comprising a heavy chain variable region having the amino acid sequence set forth in residues 20-137 of SEQ ID NO:2 and a light chain variable region having the amino acid sequence set forth in residues 21-132 of SEQ ID NO:12.
23. The method of claim 22 , wherein the antibody is a chimeric, humanized, or fully human antibody.
24. The method of claim 23 , wherein the antibody is a humanized antibody.
25. The method of claim 24 , wherein the humanized antibody comprises an effector domain of a human IgM or IgG antibody.
26. The method of claim 25 , wherein the IgG antibody is of the human IgG1 subtype.
27. The method of claim 22 , wherein the antibody comprises a human constant region.
28. The method of claim 1 , wherein the antibody competes for binding to CD70 with a second antibody comprising a heavy chain variable region having the amino acid sequence set forth in residues 20-137 of SEQ ID NO:22 and a light chain variable region having the amino acid sequence set forth in residues 21-132 of SEQ ID NO:32.