Method for treating glioblastoma using antibodies binding to the extracellular domain of the receptor tyrosine kinase ALK
View Patent ↗The present invention concerns an antibody specific for human ALK (Anaplastic Lymphoma Kinase), in particular a scFv, a nucleic acid sequence encoding it, its production and its use as a pharmaceutical or for diagnostic purposes. Said antibody is suitable for the local treatment of tumors, in particular glioblastoma.
1. A method for the treatment of glioblastoma in a subject suffering therefrom comprising administering to the subject a monoclonal antibody or antigen binding fragment thereof, wherein said antibody or fragment specifically binds human ALK protein, said antibody comprising a heavy chain variable region (VH) domain and a light chain variable region (VL) domain, said heavy chain variable region domain comprising the 3 CDRs in SEQ ID NO: 4 and said light chain variable region domain comprising the 3 CDRs in SEQ ID NO:5, thereby treating glioblastoma in the subject.
2. A method for the treatment of glioblastoma in a subject suffering therefrom, comprising administering to the subject an monoclonal antibody or antigen binding fragment thereof, wherein said antibody or fragment specifically binds human ALK protein, said antibody comprising a heavy chain variable region domain comprising the sequence of SEQ ID NO:4 and a light chain variable region domain comprising the sequence of SEQ ID NO:5, thereby treating glioblastoma in the subject.
3. The method of claim 1 , wherein the antibody is administered in combination with an anticancer agent.
4. The method of claim 3 , wherein the anticancer agent is methotrexate.
5. The method of claim 1 , wherein the monoclonal antibody or fragment is selected from the group consisting of a single chain antibody (scFv), a Fab fragment, an IgG antibody and an IgM antibody.
6. The method of claim 1 , said antibody or fragment having a binding affinity for the ALK epitope characterized by a K.sub.d of 30 nM or less.
7. The method of claim 1 , said antibody or fragment having a binding affinity for the ALK epitope characterized by a K.sub.d of less than 3 nM.
8. The method of claim 1 , wherein the VH and VL domains comprise frameworks that are stable and soluble so as to be functional in an intracellular reducing environment.
9. The method of claim 1 , wherein the antibody or fragment thereof is derived from framework 4.4 (SEQ ID NO: 20).
10. The method of claim 1 , wherein the VH domain is a H3 VH domain and the VL domain is a lambda1 VL domain.
11. The method of claim 2 , wherein the antibody is administered in combination with an anticancer agent.
12. The method of claim 11 , wherein the anticancer agent is methotrexate.
13. The method of claim 2 , wherein the monoclonal antibody or fragment is selected from the group consisting of a single chain antibody (scFv), a Fab fragment, an IgG antibody and an IgM antibody.
14. The method of claim 2 , said antibody or fragment having a binding affinity for the ALK epitope characterized by a K.sub.d of 30 nM or less.
15. The method of claim 2 , said antibody or fragment having a binding affinity for the ALK epitope characterized by a K.sub.d of less than 3 nM.
16. The method of claim 2 , said antibody comprising the structure NH.sub.2-VL-linker-VH—COOH or NH.sub.2-VH-linker-VL-COOH, wherein the linker has the sequence GGGGSGGGGSGGGGSSGGGS (SEQ ID NO: 16).