Anti-
Use of a monoclonal antibody directed against the extracellular domain of hepatocyte growth factor is disclosed for the preparation of a medicament for the treatment of tumors and/or metastases and of a diagnostic tool for detecting neoplastic cells as well as vectors comprising at least a portion of the nucleotide sequence encoding the anti-Met monoclonal antibody, products containing the anti-Met monoclonal antibody and/or at least one fragment thereof and at least one kinase inhibitor.
1. A method of treating a tumor or tumor metastases comprising administering to a patient in need thereof:
i) the anti-Met monoclonal antibody AntiMET-R,
ii) a fragment containing the epitope binding region of the anti-Met monoclonal antibody AntiMET-R or
iii) a genetically engineered antibody containing the complementarity determining regions (CDRs) of the anti-Met monoclonal antibody AntiMET-R, wherein CDR-H1 is SEQ ID NO.:8, CDR-H2 is SEQ ID NO.:9, CDR-H3 is SEQ ID NO.:10, CDR-L1 is SEQ ID NO.:11, CDR-L2 is SEQ ID NO.:12 and CDR-L3 is SEQ ID NO.:13
in an amount sufficient to effect said treatment, wherein said antibody AntiMET-R is produced by the hybridoma cell line ICLC PD 05006.
2. The method according to claim 1 , wherein said antibody, said fragment or said genetically engineered antibody is in the form of soluble protein.
3. The method according to claim 1 , wherein said antibody or said genetically engineered antibody is produced by a method selected from the group consisting of DNA recombinant technique, solid phase synthesis, and liquid phase synthesis.
4. The method according to claim 1 , wherein said fragment is selected from the group consisting of Fab, F(ab′) 2 , Fab′, Fv, scFv, and a peptide containing the epitope binding region.
5. The method according to claim 1 , wherein said fragment is produced by a method selected from the group consisting of proteolytic cleavage of said antibody, DNA recombinant technique, solid phase synthesis, and liquid phase synthesis.
6. The method according to claim 1 , wherein said administration is by injection or by infusion.
7. The method according to claim 1 , wherein said tumor is a colorectal tumor or a liver tumor.
8. The method according to claim 1 wherein said method further comprises administering to said patient at least one kinase inhibitor.
9. The method according to claim 8 wherein said at least one kinase inhibitor is selected from the group consisting of K252A staurosporin analogue; (3Z)-5-[(2,6-dichlorobenzyl)sulfonyl]-3-[(3,5-dimethyl-4-{[(2R)-2-(pyrrolidin-1-ylmethy)pyrrolidin-1-yl]carbonyl}-1H-pyrrol-2-yl)methylene]-1,3-dihydro-2H-indol-2-one;[(3Z)-N-(3-chlorophenyl)-3-({3,5-dimethyl-4-[(4-methylpiperazin-1-yl)carbonyl]-1H-pyrrol-2-yl{methylene)-N-methyl-2-oxoindoline-5-sulfonamide};[(3Z)-5-(2,3-dihydro-1H-indol-1-ylsulfonyl)-3-({3,5-dimethyl-4-[(4-methylpiperazin-1-yl)carbonyl]-1H-pyrrol-2-yl}methylene)-1,3-dihydro-2H -indol-2- one]; and [(3Z)-N-(3-chlorophenyl)-3-{[3,5-dimethyl-4-(3-morpholin-4-ylpropyl)-1H-pyrrol-2-yl]methylenel}-N-methyl-2-oxoindoline-5-sulfonamide].
10. The method according to claim 9 wherein said at least one kinase inhibitor is administered in combination with said antibody, said fragment or said genetically engineered antibody.
11. The method according to claim 9 wherein said at least one kinase inhibitor is administered separately from said antibody, said fragment or said genetically engineered antibody.
12. The method according to claim 9 wherein said at least one kinase inhibitor is administered simultaneously with said antibody, said fragment or said genetically engineered antibody.
13. The method according to claim 9 wherein said at least one kinase inhibitor and said antibody, said fragment or said genetically engineered antibody are administered sequentially.