Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Targeting the oncogenic Met receptor by antibodies and gene therapy

Oncogene volume 34, pages 1883–1889 (2015)Cite this article

Subjects

Abstract

The receptor for hepatocyte growth factor (HGF), a tyrosine kinase encoded by the Met oncogene, has a crucial role in cancer growth, invasion and metastasis. It is a validated therapeutic target for ‘personalized’ treatment of a number of malignancies. Therapeutic tools prompting selective, robust and highly effective Met inhibition potentially represent a major step in the battle against cancer. Antibodies targeting either Met or its ligand HGF, although challenging, demonstrate to be endowed with promising features. Here we briefly review and discuss the state of the art in the field.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Stratton MR, Campbell PJ, Futreal PA . The cancer genome. Nature 2009; 458: 719–724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sawyers C . Targeted cancer therapy. Nature 2004; 432: 294–297.

    Article  CAS  PubMed  Google Scholar 

  3. Zwick E, Bange J, Ullrich A . Receptor tyrosine kinase signalling as a target for cancer intervention strategies. Endocr Relat Cancer 2001; 8: 161–173.

    Article  CAS  PubMed  Google Scholar 

  4. Trusolino L, Comoglio PM . Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer 2002; 2: 289–300.

    Article  CAS  PubMed  Google Scholar 

  5. Schmidt L, Duh FM, Chen F, Kishida T, Glenn G, Choyke P et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 1997; 16: 68–73.

    Article  CAS  PubMed  Google Scholar 

  6. Di Renzo MF, Olivero M, Martone T, Maffe A, Maggiora P, Stefani AD et al. Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene 2000; 19: 1547–1555.

    Article  CAS  PubMed  Google Scholar 

  7. Stella GM, Benvenuti S, Gramaglia D, Scarpa A, Tomezzoli A, Cassoni P et al. MET mutations in cancers of unknown primary origin (CUPs). Hum Mutat 2011; 32: 44–50.

    Article  CAS  PubMed  Google Scholar 

  8. 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: 1039–1043.

    Article  CAS  PubMed  Google Scholar 

  9. Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc Natl Acad Sci USA 2007; 104: 20932–20937.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bardelli A, Corso S, Bertotti A, Hobor S, Valtorta E, Siravegna G et al. Amplification of the MET receptor drives resistance to anti-EGFR therapies in colorectal cancer. Cancer Discov 2013; 3: 658–673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Catenacci DV, Henderson L, Xiao SY, Patel P, Yauch RL, Hegde P et al. Durable complete response of metastatic gastric cancer with anti-Met therapy followed by resistance at recurrence. Cancer Discov 2011; 1: 573–579.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lennerz JK, Kwak EL, Ackerman A, Michael M, Fox SB, Bergethon K et al. MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib. J Clin Oncol 2011; 29: 4803–4810.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Comoglio PM, Giordano S, Trusolino L . Drug development of MET inhibitors: targeting oncogene addiction and expedience. Nat Rev Drug Discov 2008; 7: 504–516.

    Article  CAS  PubMed  Google Scholar 

  14. Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM . Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 2003; 3: 347–361.

    Article  PubMed  Google Scholar 

  15. De Bacco F, Luraghi P, Medico E, Reato G, Girolami F, Perera T et al. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J Natl Cancer Inst 2011; 103: 645–661.

    Article  CAS  PubMed  Google Scholar 

  16. De Bacco F, Casanova E, Medico E, Pellegatta S, Orzan F, Albano R et al. The MET oncogene is a functional marker of a glioblastoma stem cell subtype. Cancer Res 2012; 72: 4537–4550.

    Article  CAS  PubMed  Google Scholar 

  17. Luraghi P, Reato G, Cipriano E, Sassi F, Orzan F, Bigatto V et al. MET signaling in colon cancer stem-like cells blunts the therapeutic response to EGFR inhibitors. Cancer Res 2014; 74: 1857–1869.

    Article  CAS  PubMed  Google Scholar 

  18. Gherardi E, Birchmeier W, Birchmeier C, Vande Woude G . Targeting MET in cancer: rationale and progress. Nat Rev Cancer 2012; 12: 89–103.

    Article  CAS  PubMed  Google Scholar 

  19. Peters S, Adjei AA . MET: a promising anticancer therapeutic target. Nat Rev Clin Oncol 2012; 9: 314–326.

    Article  CAS  PubMed  Google Scholar 

  20. Toschi L, Jänne PA . Single-agent and combination therapeutic strategies to inhibit hepatocyte growth factor/MET signaling in cancer. Clin Cancer Res 2008; 14: 5941–5946.

    Article  CAS  PubMed  Google Scholar 

  21. Bell DW, Gore I, Okimoto RA, Godin-Heymann N, Sordella R, Mulloy R et al. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 2005; 37: 1315–1316.

    Article  CAS  PubMed  Google Scholar 

  22. Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. New Engl J Med 2005; 352: 786–792.

    Article  CAS  PubMed  Google Scholar 

  23. Chen LL, Trent JC, Wu EF, Fuller GN, Ramdas L, Zhang W et al. A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res 2004; 64: 5913–5919.

    Article  CAS  PubMed  Google Scholar 

  24. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001; 293: 876–880.

    Article  CAS  PubMed  Google Scholar 

  25. Di Fiore PP, Gill GN . Endocytosis and mitogenic signaling. Curr Opin Cell Biol 1999; 11: 483–488.

    Article  CAS  PubMed  Google Scholar 

  26. Peschard P, Fournier TM, Lamorte L, Naujokas MA, Band H, Langdon WY et al. Mutation of the c-Cbl TKB domain binding site on the Met receptor tyrosine kinase converts it into a transforming protein. Mol Cell 2001; 8: 995–1004.

    Article  CAS  PubMed  Google Scholar 

  27. Ponzetto C, Bardelli A, Zhen Z, Maina F, dalla Zonca P, Giordano S et al. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 1994; 77: 261–271.

    Article  CAS  PubMed  Google Scholar 

  28. Leiser D, Pochon B, Blank-Liss W, Francica P, Glück AA, Aebersold DM et al. Targeting of the MET receptor tyrosine kinase by small molecule inhibitors leads to MET accumulation by impairing the receptor downregulation. FEBS Lett 2014; 588: 653–658.

    Article  CAS  PubMed  Google Scholar 

  29. Duvvuri M, Krise JP . Intracellular drug sequestration events associated with the emergence of multidrug resistance: a mechanistic review. Front Biosci 2005; 10: 1499–1509.

    Article  CAS  PubMed  Google Scholar 

  30. Cao B, Su Y, Oskarsson M, Zhao P, Kort EJ, Fisher RJ et al. Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models. Proc Natl Acad Sci USA 2001; 98: 7443–7448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhao P, Gao C, Dykema K, Furge K, Feng Z, Cao B . Repeated hepatocyte growth factor neutralizing antibody treatment leads to HGF/SF unresponsiveness in human glioblastoma multiforme cells. Cancer Lett 2010; 291: 209–216.

    Article  CAS  PubMed  Google Scholar 

  32. Burgess T, Coxon A, Meyer S, Sun J, Rex K, Tsuruda T et al. Fully human monoclonal antibodies to hepatocyte growth factor with therapeutic potential against hepatocyte growth factor/c-Met-dependent human tumors. Cancer Res 2006; 66: 1721–1729.

    Article  CAS  PubMed  Google Scholar 

  33. Burgess TL, Sun J, Meyer S, Tsuruda TS, Elliott G, Chen Q et al. Biochemical characterization of AMG 102: a neutralizing, fully human monoclonal antibody to human and nonhuman primate hepatocyte growth factor. Mol Cancer Ther 2010; 9: 400–409.

    Article  CAS  PubMed  Google Scholar 

  34. Jun HT, Sun J, Rex K, Radinsky R, Kendall R, Coxon A et al. AMG 102, a fully human anti-hepatocyte growth factor/scatter factor neutralizing antibody, enhances the efficacy of temozolomide or docetaxel in U-87 MG cells and xenografts. Clin Cancer Res 2007; 13: 6735–6742.

    Article  CAS  PubMed  Google Scholar 

  35. Buchanan IM, Scott T, Tandle AT, Burgan WE, Burgess TL, Tofilon PJ et al. Radiosensitization of glioma cells by modulation of Met signalling with the hepatocyte growth factor neutralizing antibody, AMG102. J Cell Mol Med 2011; 15: 1999–2006.

    Article  CAS  PubMed  Google Scholar 

  36. Kim KJ, Wang L, Su YC, Gillespie GY, Salhotra A, Lal B et al. Systemic anti-hepatocyte growth factor monoclonal antibody therapy induces the regression of intracranial glioma xenografts. Clin Cancer Res 2006; 12: 1292–1298.

    Article  CAS  PubMed  Google Scholar 

  37. Okamoto W, Okamoto I, Tanaka K, Hatashita E, Yamada Y, Kuwata K et al. TAK-701, a humanized monoclonal antibody to hepatocyte growth factor, reverses gefitinib resistance induced by tumor-derived HGF in non-small cell lung cancer with an EGFR mutation. Mol Cancer Ther 2010; 9: 2785–2792.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Houghton PJ, Kurmasheva RT, Kolb EA, Wu J, Gorlick R, Maris JM et al. Initial testing (Stage 1) of TAK-701, a humanized hepatocyte growth factor binding antibody, by the pediatric preclinical testing program. Pediatr Blood Cancer 2014; 61: 380–382.

    Article  CAS  PubMed  Google Scholar 

  39. Mittra ES, Fan-Minogue H, Lin FI, Karamchandani J, Sriram V, Han M et al. Preclinical efficacy of the anti-hepatocyte growth factor antibody ficlatuzumab in a mouse brain orthotopic glioma model evaluated by bioluminescence, PET, and MRI. Clin Cancer Res 2013; 19: 5711–5721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kim K, Hur Y, Ryu EK, Rhim JH, Choi CY, Baek CM et al. A neutralizable epitope is induced on HGF upon its interaction with its receptor cMet. Biochem Biophys Res Commun 2007; 354: 115–121.

    Article  CAS  PubMed  Google Scholar 

  41. Vosjan MJ, Vercammen J, Kolkman JA, Stigter-van Walsum M, Revets H, van Dongen GA . Nanobodies targeting the hepatocyte growth factor: potential new drugs for molecular cancer therapy. Mol Cancer Ther 2012; 11: 1017–1025.

    Article  CAS  PubMed  Google Scholar 

  42. Bussolino F, Di Renzo MF, Ziche M, Bocchietto E, Olivero M, Naldini L et al. Hepatocyte growth factor is a potent angiogenic factor which stimulates endothelial cell motility and growth. J Cell Biol 1992; 119: 629–641.

    Article  CAS  PubMed  Google Scholar 

  43. Wu X, Chen X, Zhou Q, Li P, Yu B, Li J et al. Hepatocyte growth factor activates tumor stromal fibroblasts to promote tumorigenesis in gastric cancer. Cancer Lett 2013; 335: 128–135.

    Article  CAS  PubMed  Google Scholar 

  44. Galimi F, Cottone E, Vigna E, Arena N, Boccaccio C, Giordano S et al. Hepatocyte growth factor is a regulator of monocyte-macrophage function. J Immunol 2001; 166: 1241–1247.

    Article  CAS  PubMed  Google Scholar 

  45. Wang R, Zhang J, Chen S, Lu M, Luo X, Yao S et al. Tumor-associated macrophages provide a suitable microenvironment for non-small lung cancer invasion and progression. Lung Cancer 2011; 74: 188–196.

    Article  PubMed  Google Scholar 

  46. 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: 437–446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Schöffski P, Garcia JA, Stadler WM, Gil T, Jonasch E, Tagawa ST et al. A phase II study of the efficacy and safety of AMG 102 in patients with metastatic renal cell carcinoma. BJU Int 2011; 108: 679–686.

    PubMed  Google Scholar 

  48. Martin LP, Sill M, Shahin MS, Powell M, Disilvestro P, Landrum LM et al. A phase II evaluation of AMG 102 (rilotumumab) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 2013; 132: 526–530.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Ryan CJ, Rosenthal M, Ng S, Alumkal J, Picus J, Gravis G et al. Targeted MET inhibition in castration-resistant prostate cancer: a randomized phase II study and biomarker analysis with rilotumumab plus mitoxantrone and prednisone. Clin Cancer Res 2013; 19: 215–224.

    Article  CAS  PubMed  Google Scholar 

  50. Rosen PJ, Sweeney CJ, Park DJ, Beaupre DM, Deng H, Leitch IM et al. A phase Ib study of AMG 102 in combination with bevacizumab or motesanib in patients with advanced solid tumors. Clin Cancer Res 2010; 16: 2677–2687.

    Article  CAS  PubMed  Google Scholar 

  51. D'Arcangelo M, Cappuzzo F . Focus on the potential role of ficlatuzumab in the treatment of non-small cell lung cancer. Biologics 2013; 7: 61–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. van der Horst EH, Chinn L, Wang M, Velilla T, Tran H, Madrona Y et al. Discovery of fully human anti-MET monoclonal antibodies with antitumor activity against colon cancer tumor models in vivo. Neoplasia 2009; 11: 355–364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Greenall SA, Gherardi E, Liu Z, Donoghue JF, Vitali AA, Li Q et al. Non-agonistic bivalent antibodies that promote c-MET degradation and inhibit tumor growth and others specific for tumor related c-MET. PLoS ONE 2012; 7: e34658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lee JM, Kim B, Lee SB, Jeong Y, Oh YM, Song YJ et al. Cbl-independent degradation of Met: ways to avoid agonism of bivalent Met-targeting antibody. Oncogene 2014; 33: 34–43.

    Article  CAS  PubMed  Google Scholar 

  55. Schmidt Slørdahl T, Denayer T, Helen Moen S, Standal T, Børset M, Ververken C et al. Anti-c-MET Nanobody—a new potential drug in multiple myeloma treatment. Eur J Haematol 2013; 91: 399–410.

    Article  Google Scholar 

  56. Zeng W, Yan L, Peek V, Wortinger M, Tetreault J, Xia J et al. c-Met antibody LY2875358 (LA480) shows differential antitumor effects in non-small cell lung cancer. Cancer Res 2012; 72 (Suppl 1) Abstract 2734).

  57. Goldman JW, Rosen LS, Algazi AP, Turner PK, Wacheck V, Tuttle J et al. First-in-human dose escalation study of LY2875358 (LY), a bivalent MET antibody, as monotherapy and in combination with erlotinib (E) in patients with advanced cancer. J Clin Onc 2013; 31 (May 20 Suppl) (a)bstract 8093).

  58. Goetsch L, Broussas M, Fabre-Lafay S, Robert A, Lepecquet AM, Gonzalez A et al. h224G11, a humanized whole antibody targeting the c-Met receptor, induces c-Met down-regulation and triggers ADCC functions. Cancer Res 2010; 70 (Suppl 1) (a)bstract 2448).

    Article  Google Scholar 

  59. 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.

    Article  CAS  PubMed  Google Scholar 

  60. Merchant AM, Zhu Z, Yuan JQ, Goddard A, Adams CW, Presta LG et al. An efficient route to human bispecific IgG. Nat Biotechnol 1998; 16: 677–681.

    Article  CAS  PubMed  Google Scholar 

  61. Merchant M, Ma X, Maun HR, Zheng Z, Peng J, Romero M et al. Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent. Proc Natl Acad Sci USA 2013; 110: E2987–E2996.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Martens T, Schmidt NO, Eckerich C, Fillbrandt R, Merchant M, Schwall R et al. A novel one-armed anti-c-Met antibody inhibits glioblastoma growth in vivo. Clin Cancer Res 2006; 12 (20 Pt 1): 6144–6152.

    Article  CAS  PubMed  Google Scholar 

  63. Jin H, Yang R, Zheng Z, Romero M, Ross J, Bou-Reslan H et al. MetMAb, the one-armed 5D5 anti-c-Met antibody, inhibits orthotopic pancreatic tumor growth and improves survival. Cancer Res 2008; 68: 4360–4368.

    Article  CAS  PubMed  Google Scholar 

  64. Xin Y, Jin D, Eppler S, Damico-Beyer LA, Joshi A, Davis JD et al. Population pharmacokinetic analysis from phase I and phase II studies of the humanized monovalent antibody, onartuzumab (MetMAb), in patients with advanced solid tumors. J Clin Pharmacol 2013; 53: 1103–1111.

    Article  CAS  PubMed  Google Scholar 

  65. Bendell JC, Ervin TJ, Gallinson D, Singh J, Wallace JA, Saleh MN et al. Treatment rationale and study design for a randomized, double-blind, placebo-controlled phase II study evaluating onartuzumab (MetMAb) in combination with bevacizumab plus mFOLFOX-6 in patients with previously untreated metastatic colorectal cancer. Clin Colorectal Cancer 2013; 12: 218–222.

    Article  CAS  PubMed  Google Scholar 

  66. Sadiq AA, Salgia R . MET as a possible target for non-small-cell lung cancer. J Clin Oncol 2013; 31: 1089–1096.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Castoldi R, Ecker V, Wiehle L, Majety M, Busl-Schuller R, Asmussen M et al. A novel bispecific EGFR/Met antibody blocks tumor-promoting phenotypic effects induced by resistance to EGFR inhibition and has potent antitumor activity. Oncogene 2013; 32: 5593–5601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Prat M, Crepaldi T, Pennacchietti S, Bussolino F, Comoglio PM . Agonistic monoclonal antibodies against the Met receptor dissect the biological responses to HGF. J Cell Sci 1998; 111: 237–247.

    CAS  PubMed  Google Scholar 

  69. Vigna E, Pacchiana G, Mazzone M, Chiriaco C, Fontani L, Basilico C et al. ‘Active’ cancer immunotherapy by anti-Met antibody gene transfer. Cancer Res 2008; 68: 9176–9183.

    Article  CAS  PubMed  Google Scholar 

  70. Petrelli A, Circosta P, Granziero L, Mazzone M, Pisacane A, Fenoglio S et al. Ab-induced ectodomain shedding mediates hepatocyte growth factor receptor down-regulation and hampers biological activity. Proc Natl Acad Sci USA 2006; 103: 5090–5095.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Edwards DR, Handsley MM, Pennington CJ . The ADAM metalloproteinases. Mol Aspects Med 2008; 29: 258–289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Schelter F, Kobuch J, Moss ML, Becherer JD, Comoglio PM, Boccaccio C et al. A disintegrin and metalloproteinase-10 (ADAM-10) mediates DN30 antibody-induced shedding of the met surface receptor. J Biol Chem 2010; 285: 26335–26340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Foveau B, Ancot F, Leroy C, Petrelli A, Reiss K, Vingtdeux V et al. Down-regulation of the met receptor tyrosine kinase by presenilin-dependent regulated intramembrane proteolysis. Mol Biol Cell 2009; 20: 2495–2507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ancot F, Leroy C, Muharram G, Lefebvre J, Vicogne J, Lemiere A et al. Shedding-generated Met receptor fragments can be routed to either the proteasomal or the lysosomal degradation pathway. Traffic 2012; 13: 1261–1272.

    Article  CAS  PubMed  Google Scholar 

  75. Michieli P, Mazzone M, Basilico C, Cavassa S, Sottile A, Naldini L et al. Targeting the tumor and its microenvironment by a dual-function decoy Met receptor. Cancer Cell 2004; 6: 61–73.

    Article  CAS  PubMed  Google Scholar 

  76. Bardelli C, Sala M, Cavallazzi U, Prat M . Agonist Met antibodies define the signalling threshold required for a full mitogenic and invasive program of Kaposi's Sarcoma cells. Biochem Biophys Res Commun 2005; 334: 1172–1279.

    Article  CAS  PubMed  Google Scholar 

  77. 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: 36149–36157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Gillet JP, Macadangdang B, Fathke RL, Gottesman MM, Kimchi-Sarfaty C . The development of gene therapy: from monogenic recessive disorders to complex diseases such as cancer. Methods Mol Biol 2009; 542: 5–54.

    Article  CAS  PubMed  Google Scholar 

  79. Vigna E, Naldini L . Lentiviral vectors: excellent tools for experimental gene transfer and promising candidates for gene therapy. J Gene Med 2000; 2: 308–316.

    Article  CAS  PubMed  Google Scholar 

  80. Aiuti A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 2013; 341: 1233151.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 2013; 341: 1233158.

    Article  PubMed  Google Scholar 

  82. Vigna E, Pacchiana G, Chiriaco C, Cignetto S, Fontani L, Michieli P et al. Targeted therapy by gene transfer of a monovalent antibody fragment against the Met oncogenic receptor. J Mol Med (Berl) 2014; 92: 65–76.

    Article  CAS  Google Scholar 

  83. Bertotti A, Trusolino L . From bench to bedside: does preclinical practice in translational oncology need some rebuilding? J Natl Cancer Inst 2013; 105: 1426–1427.

    Article  PubMed  Google Scholar 

  84. Perk LR, Stigter-van Walsum M, Visser GW, Kloet RW, Vosjan MJ, Leemans CR et al. Quantitative PET imaging of Met-expressing human cancer xenografts with 89Zr-labelled monoclonal antibody DN30. Eur J Nucl Med Mol Imaging 2008; 35: 1857–1867.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The original work performed by the authors was supported by an IG grant from the AIRC (Italy) no. 11852 and by a research contract between Metheresis Translational Research SA and the University of Torino. The images are unpublished experiments of Dr Letizia Lanzetti. The invaluable secretarial help of Antonella Cignetto is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Oncology, University of Torino, and Candiolo Cancer Institute, FPO-IRCCS, Candiolo (TO), Italy,

    E Vigna & P M Comoglio

Authors
  1. E Vigna
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P M Comoglio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to E Vigna or P M Comoglio.

Ethics declarations

Competing interests

PMC and EV are authors of the international patent WO2007090807 (‘Anti-met monoclonal antibody, fragments and vectors thereof …’) owned by Metheresis Translational Research SA (Switzerland); The University of Torino received financial support from Metheresis and PMC is a consultant. The company did not interfere at all in the preparation and in the submission of the review article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vigna, E., Comoglio, P. Targeting the oncogenic Met receptor by antibodies and gene therapy. Oncogene 34, 1883–1889 (2015). https://doi.org/10.1038/onc.2014.142

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2014.142

This article is cited by

Search

Advanced search

Quick links