Therapeutic use of anti-tweak receptor antibodies

1. A monoclonal anti-TweakR antibody or an antigen binding fragment thereof, comprising the following six CDRs:

V H CDR #1 is: S Y W M S (SEQ ID NO:13);

V H CDR #2 is: E I R L K S D N Y A T H Y A E S V K G (SEQ ID NO:19);

V H CDR #3 is: Y Y A D A M D Y (SEQ ID NO:25);

V L CDR #1 is: A A S Q S V S T S S Y S Y M H (SEQ ID NO:66);

V L CDR #2 is: Y A S N L E S (SEQ ID NO:72); and

V L CDR #3 is: Q H S W E I P Y T (SEQ ID NO:78).

2. The monoclonal anti-TweakR antibody or antigen binding fragment of claim 1 , which comprises a V H region comprising SEQ ID NO:3 and a V L region comprising SEQ ID NO:4.

3. The monoclonal anti-TweakR antibody or antigen binding fragment of claim 2 , which is an IgG 1 .

4. The monoclonal anti-TweakR antibody or antigen binding fragment of claim 1 , which comprises a V H region comprising SEQ ID NO:5 and a V L region comprising SEQ ID NO:6.

5. The monoclonal anti-TweakR antibody or antigen binding fragment of claim 1 which is conjugated to an effector moiety and/or a detectable label.

6. The monoclonal anti-TweakR antibody or antigen binding fragment of claim 5 which is conjugated to a detectable label.

7. The monoclonal anti-TweakR antibody or antigen binding fragment of claim 6 , wherein the detectable label is a radioactive compound, a fluorescent compound, an enzyme, a substrate or an epitope tag.

8. The monoclonal anti-TweakR antibody or antigen binding fragment of claim 5 , which is conjugated to an effector moiety.

9. The monoclonal anti-TweakR antibody or antigen binding fragment of claim 8 , wherein the effector moiety is a cytotoxic agent.

10. The monoclonal anti-TweakR antibody or antigen binding fragment of claim 9 , wherein the cytotoxic agent is a toxin, a chemotherapeutic agent, an immune modulator, or a radioisotope.

11. The monoclonal anti-TweakR antibody or antigen binding fragment of claim 1 which is humanized.

12. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier or diluent.

13. A method of treating a subject having a solid tumor, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 12 .

14. The method of claim 13 , further comprising administering to the subject a second therapeutic agent selected from the group consisting of a targeted therapeutic agent, a conventional chemotherapy agent, and a hormonal therapy agent.

15. The method of claim 14 , wherein the second therapeutic agent is a conventional chemotherapy agent.

16. The method of claim 13 , wherein the solid tumor is a bladder cancer, a breast cancer, a colorectal cancer, a lung cancer, a melanoma, a pancreatic cancer, an ovarian cancer, a renal cancer, a head and neck cancer, an esophageal cancer, a uterine cancer, a stomach cancer, a cervical cancer, a glioblastoma, or a sarcoma.

17. The method of claim 16 , wherein the solid tumor is a colorectal cancer.

18. The method of claim 16 , wherein the solid tumor is a pancreatic cancer.

19. The method of claim 16 , wherein the solid tumor is a breast cancer.

20. The method of claim 13 , in which the solid tumor has a mutation in a gene selected from the group consisting of BRAF, KRAS, PTEN, and PIK3CA.

21. The method of claim 20 , in which the solid tumor has a mutation in PIK3 CA.