A highly potent and specific MET therapeutic protein antagonist with both ligand-dependent and ligand-independent activity

Molecular Cancer Therapeutics

Volumn 12, Issue 11, 2013, Pages 2459-2471

  Olwill, Shane A ^a   Joffroy, Christian ^a   Gille, Hendrik ^a   Vigna, Elisa ^b   Matschiner, Gabriele ^a   Allersdorfer, Andrea ^a   Lunde, Bradley M ^a   Jaworski, Jakub ^c   Burrows, James F ^c   Chiriaco, Cristina ^b   Christian, Hans Jürgen ^a   Hülsmeyer, Martin ^a   Trentmann, Stefan ^a   Jensen, Kristian ^a   Hohlbaum, Andreas M ^a   Audoly, Laurent ^a  

^a Pieris Pharmaceuticals GmbH   (Germany)

^b Dept of Radiology   (Italy)

^c QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; LIGAND; PRS 110; SCATTER FACTOR RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; CANCER CELL CULTURE; CANCER INHIBITION; CELL PROLIFERATION; CONFOCAL MICROSCOPY; CONTROLLED STUDY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; ENDOSOME; EPITOPE MAPPING; FEMALE; HALF LIFE TIME; HUMAN; HUMAN CELL; IMMUNOGENICITY; IN VIVO STUDY; LYSOSOME; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; TUMOR VOLUME; TUMOR XENOGRAFT;

AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; CELL LINE, TUMOR; CHO CELLS; CRICETULUS; DOSE-RESPONSE RELATIONSHIP, DRUG; EPITOPE MAPPING; FEMALE; HEPATOCYTE GROWTH FACTOR; HT29 CELLS; HUMAN UMBILICAL VEIN ENDOTHELIAL CELLS; HUMANS; LIGANDS; LIPOCALINS; MICE; MICE, INBRED BALB C; MICE, NUDE; NEOPLASMS, EXPERIMENTAL; PROTEIN KINASE INHIBITORS; PROTEINS; PROTO-ONCOGENE PROTEINS C-MET; SIGNAL TRANSDUCTION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84887495001     PISSN: 15357163     EISSN: 15388514     Source Type: Journal    
DOI: None     Document Type: Article

References (46)

1. Mach KE, Furge KA, Albright CF. Loss of Rhb1, a Rheb-related GTPase in fission yeast, causes growth arrest with a terminal phenotype similar to that caused by nitrogen starvation. Genetics 2000;155:611-22.
2. Comoglio PM, Giordano S, Trusolino L. Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov 2008;7:504-16.
3. Trusolino L, Comoglio PM. Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer 2002;2:289-300.
4. Weidner KM, Arakaki N, Hartmann G, Vandekerckhove J, Weingart S, Rieder H, et al. Evidence for the identity of human scatter factor and human hepatocyte growth factor.Proc Natl Acad Sci USA 1991;88: 7001-5.
5. Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, et al. Identification of the hepatocyte growth factor receptor as the MET proto-oncogene product. Science 1991;251:802-4.
6. Gherardi E, Stoker M. Hepatocyte growth factor-scatter factor: mitogen, motogen, and met. Cancer Cells 1991;3:227-32.
7. Naldini L, Weidner KM, Vigna E, Gaudino G, Bardelli A, Ponzetto C, et al. Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. EMBO J 1991;10:2867-78.
8. Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. Met, metastasis, motility and more. Nat Rev Mol Cell Biol 2003;4:915-25.
9. Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G. Targeting MET in cancer: rationale and progress. Nat Rev Cancer 2012;12: 89-103.
10. Ichimura E, Maeshima A, Nakajima T, Nakamura T. Expression of MET/ HGF receptor in human non-small cell lung carcinomas in vitro and in vivo and its prognostic significance. Jpn J Cancer Res 1996;87: 1063-9.
11. Götte M, Kersting C, Radke I, Kiesel L, Wülfing P. An expression signature of syndecan-1 (CD138), E-cadherin and MET is associated with factors of angiogenesis and lymphangiogenesis in ductal breast carcinoma in situ. Breast Cancer Res 2007;9:R8.
12. Garcia S, Dales JP, Charafe-Jauffret E, Carpentier-Meunier S, Andrac- Meyer L, Jacquemier J, et al. Overexpression of c-Met and of the transducers PI3K, FAK and JAK in breast carcinomas correlates with shorter survival and neoangiogenesis. Int J Oncol 2007;31:49-58.
13. Kammula US, Kuntz EJ, Francone TD, Zeng Z, Shia J, Landmann RG, et al. Molecular co-expression of the MET oncogene and hepatocyte growth factor in primary colon cancer predicts tumor stage and clinical outcome. Cancer Lett 2007;248:219-28.
14. Miyata Y, Kanetake H, Kanda S. Presence of phosphorylated hepatocyte growth factor receptor/c-Met is associated with tumor progression and survival in patients with conventional renal cell carcinoma. Clin Cancer Res 2006;12:4876-81.
15. Dulak AM, Gubish CT, Stabile LP, Henry C, Siegfried JM. HGFindependent potentiation of EGFR action by MET. Oncogene 2011; 30:3625-35.
16. Mitra AK, Sawada K, Tiwari P, Mui K, Gwin K, Lengyel E. Ligandindependent activation of MET by fibronectin and a(5)b(1)-integrin regulates ovarian cancer invasion and metastasis. Oncogene 2011;30: 1566-76.
17. McDermott U, Pusapati RV, Christensen JG, Gray NS, Settleman J. Acquired resistance to MET kinase inhibition in MET-dependent nonsmall cell lung cancer cells mediated by a switch to EGFR dependency. Cancer Res 2010;70:1625-34.
18. Bowles DW, Kessler ER, Jimeno A. Multi-targeted tyrosine kinase inhibitors in clinical development: focus on XL-184 (cabozantinib). Drugs Today (Barc) 2011;47:857-68.
19. Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, et al. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol 2011;29: 2660-6.
20. Santoro A, Rimassa L, Borbath I, Daniele B, Salvagni S, Van Laethem JL, et al. Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase 2 study. Lancet Oncol 2013;14:55-63.
21. Wagner AJ, Goldberg JM, Dubois SG, Choy E, Rosen L, Pappo A, et al. Tivantinib (ARQ 197), a selective inhibitor of MET, in patients with microphthalmia transcription factor-associated tumors: results of a multicenter phase 2 trial. Cancer 2012;118:5894-902.
22. Ou SH, Kwak EL, Siwak-Tapp C, Dy J, Bergethon K, Clark JW, et al. Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification. J Thorac Oncol 2011;6:942-6.
23. Wen PY, Schiff D, Cloughesy TF, Raizer JJ, Laterra J, Smitt M, et al. A phase II study evaluating the efficacy and safety of AMG 102 (rilotumumab) in patients with recurrent glioblastoma. Neuro Oncol 2011;13:437-46.
24. Gordon MS, Sweeney CS, Mendelson DS, Eckhardt SG, Anderson A, Beaupre DM, et al. Safety, pharmacokinetics, and pharmacodynamics of AMG 102, a fully human hepatocyte growth factor-neutralizing monoclonal antibody, in a first-in-human study of patients with advanced solid tumors. Clin Cancer Res 2010;16:699-710.
25. Pacchiana G, Chiriaco C, Stella MC, Petronzelli F, De Santis R, Galluzzo M, et al. Monovalency unleashes the full therapeutic potential of the DN-30 anti-Met antibody. J Biol Chem 2010;285:36149-57.
26. Martens T, Schmidt NO, Eckerich C, Fillbrandt R, Merchant M, Schwall R, et al. A novel one-armed anti-MET antibody inhibits glioblastoma growth in vivo. Clin Cancer Res 2006;12:6144-52.
27. Surati M, Patel P, Peterson A, Salgia R. Role of MetMAb (OA-5D5) in MET active lung malignancies. Expert Opin Biol Ther 2011;11: 1655-62.
28. Spigel DR, Ervin TJ, Ramlau R, Daniel DB, Goldschmidt JH, Krzakowski M, et al. Randomized phase 2 multicenter double-blind placebo- controlled study evaluating MetMAb, an antibody to Met receptor, in combination with erlotinib, in patients with advanced non-smallcell lung cancer. In: Proceedings of the 35th ESMO Conference, Milan, Italy, October 8-12, 2010.
29. Skerra A. Lipocalins as a scaffold. Biochim. Biophys. Acta 2000;1482: 337-50.
30. Skerra A. Alternative binding proteins: anticalins-harnessing the structural plasticity of the lipocalin ligand pocket to engineer novel binding activities. FEBS J 2008;275:2677-83.
31. Schonfeld D, Matschiner G, Chatwell L, Trentmann S, Gille H, Hulsmeyer M, et al. An engineered lipocalin specific for CTLA-4 reveals a combining site with structural and conformational features similar to antibodies. Proc Natl Acad Sci USA 2009;106:8198-203.
32. Timmerman P, Puijk WC, Meloen RH. Functional reconstruction and synthetic mimicry of a conformational epitope using CLIPS technology. J Mol Recognit 2007;20:283-99.
33. Slootstra JW, Puijk WC, Ligtvoet GJ, Langeveld JP, Meloen RH. Structural aspects of antibody-antigen interaction revealed through small random peptide libraries. Mol Divers 1996;1:87-96.
34. Mross K, Fischer R, Richly H, Scharr D, Buechert M, Stern A, et al. First in human phase I study of PRS-050 (angiocal), a VEGF-A targeting Anticalin, in patients with advanced solid tumors: results of a dose escalation study. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A212.
35. Matschiner G, Hohlbaum A, Huelsmeyer M, Trentmann S. Muteins of tear lipocalin having high affinity tohuman MET receptor tyrosine kinase and methods for obtaining same. World Patent WO2009095447. 2009 Aug 6.
36. Breustedt DA, Korndörfer IP, Redl B, Skerra A. The 1.8-A crystal structure of human tear lipocalin reveals an extended branched cavity with capacity for multiple ligands. J Biol Chem 2005;280:484-93.
37. Schwall RH, Adams CW, Zheng Z, Romero M, Mai E, Moffat B, et al. Inhibition of cMet activation by a one-armed antibody. In: Proceedings of the 95th American Association of Cancer Research Annual Meeting; 2004 March 27-31; Orlando, Florida. AACR, 2004;Volume 45; Abstract nr 1424.
38. Kong-Beltran M, Stamos J, Wickramasinghe D. The Sema domain of Met is necessary for receptor dimerization and activation. Cancer Cell 2004;6:75-84.
39. Stamos J, Lazarus RA, Yao X, Kirchhofer D, Wiesmann C. Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor. EMBO J 2004;23:2325-35.
40. Basilico C, Arnesano A, Galluzzo M, Comoglio PM, Michieli P. A high affinity hepatocyte growth factor-binding site in the immunoglobulinlike region of Met. J Biol Chem 2008;283:21267-77.
41. Gherardi E, Youles ME, Miguel RN, Blundell TL, Iamele L, Gough J, et al. Functional map and domain structure of MET, the product of the MET protooncogene and receptor for hepatocyte growth factor/scatter factor. Proc Natl Acad Sci U S A 2003;100:12039-44.
42. Niemann HH, Jäger V, Butler PJ, van den Heuvel J, Schmidt S, Ferraris D, et al. Structure of the human receptor tyrosine kinase met in complex with the Listeria invasion protein InlB. Cell 2007;130:235-46.
43. Rowland M, Tozer TN. Multiple dosing. In: Clinical pharmacokinetics and pharmacodynamics. concepts and applications. 4th ed. Lippincott Williams & Wilkins 2010;11:293-329.
44. Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007;316:1039-43.
45. Eder JP, Vande Woude GF, Boerner SA, LoRusso PM. Novel therapeutic inhibitors of the c-Met signaling pathway in cancer. Clin Cancer Res 2009;15:2207-14.
46. Hammond DE, Urbé S, Vande WoudeGF, Clague MJ. Down-regulation of MET, the receptor for hepatocyte growth factor. Oncogene 2001;20:2761-70.