Biochemical characterization of AMG 102: a neutralizing, fully human monoclonal antibody to human and nonhuman primate hepatocyte growth factor

Molecular Cancer Therapeutics
Teresa L BurgessRichard Kendall

Abstract

AMG 102 is a fully human monoclonal antibody that selectively targets and neutralizes hepatocyte growth factor/scatter factor (HGF/SF). A detailed biochemical and functional characterization of AMG 102 was done to support its clinical development for the treatment of cancers dependent on signaling through the HGF/SF:c-Met pathway. In competitive equilibrium binding experiments, AMG 102 bound to human and cynomolgus monkey HGF with affinities of approximately 19 pmol/L and 41 pmol/L, respectively. However, AMG 102 did not detect mouse or rabbit HGF on immunoblots. Immunoprecipitation experiments showed that AMG 102 preferentially bound to the mature, active form of HGF, and incubation of AMG 102/HGF complexes with kallikrein protease indicated that AMG 102 had no apparent effect on proteolytic processing of the inactive HGF precursor. AMG 102 inhibited human and cynomolgus monkey HGF-induced c-Met autophosphorylation in PC3 cells with IC(50) values of 0.12 nmol/L and 0.24 nmol/L, respectively. AMG 102 also inhibited cynomolgus monkey HGF-induced migration of human MDA-MB-435 cells but not rat HGF-induced migration of mouse 4T1 cells. Epitope-mapping studies of recombinant HGF molecules comprising human/mouse chimeras and human-t...Continue Reading

References

Jan 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·J S RubinP W Finch
Apr 1, 1997·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·T UekiE Okamoto
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·M JeffersG F Vande Woude
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·B CaoG F Vande Woude
May 11, 2002·Nature Reviews. Cancer·Livio Trusolino, Paolo M Comoglio
Aug 22, 2002·Nature Reviews. Cancer·Jean Paul Thiery
Jun 6, 2003·Nature·Donald P Bottaro, Lance A Liotta
Jun 26, 2003·Cancer Science·Kunio Matsumoto, Toshikazu Nakamura
Dec 20, 2003·Nature Reviews. Molecular Cell Biology·Carmen BirchmeierGeorge F Vande Woude
May 29, 2004·The EMBO Journal·Jennifer StamosChristian Wiesmann
Jun 26, 2004·The Journal of Biological Chemistry·Daniel KirchhoferRobert A Lazarus
Nov 24, 2004·Proceedings of the National Academy of Sciences of the United States of America·Carrie GraveelGeorge Vande Woude
Dec 8, 2004·Current Molecular Medicine·Pathirage G DharmawardanaDonald P Bottaro
Feb 21, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·K Jin KimJohn Laterra
Nov 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·H Toni JunTeresa L Burgess
Feb 26, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Cristina Migliore, Silvia Giordano
Apr 15, 2008·Current Opinion in Genetics & Development·Beatrice S Knudsen, George Vande Woude
May 31, 2008·Nature Reviews. Drug Discovery·Paolo M ComoglioLivio Trusolino
Jan 14, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael S GordonLia Gore

❮ Previous
Next ❯

Citations

Nov 1, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A FasoloM Broggini
Jul 23, 2013·The Cancer Journal·Sumanta K PalRobert A Figlin
Feb 22, 2012·Molecular Cancer Therapeutics·Sumanta Kumar PalDavid I Quinn
Aug 8, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·George R BlumenscheinAna M Gonzalez-Angulo
Feb 13, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ahad A Sadiq, Ravi Salgia
Jun 12, 2010·Biological Chemistry·Henry R MaunRobert A Lazarus
Feb 18, 2016·Clinical Oncology : a Journal of the Royal College of Radiologists·J LeeS J Klempner
Nov 18, 2015·Expert Opinion on Drug Metabolism & Toxicology·Louisa LoTimothy J Price
Nov 1, 2011·Expert Opinion on Investigational Drugs·Andreas VarkarisGary E Gallick
Sep 28, 2010·Expert Opinion on Investigational Drugs·Giulia M StellaPaolo M Comoglio
Dec 24, 2014·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Daniel MorgenszternRamaswamy Govindan
Jan 15, 2016·British Journal of Cancer·Srinivasa P PothulaMinoti V Apte
Jul 5, 2013·Kidney International·Oscar C Y YangPatrick J Pollard
Dec 23, 2015·Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association·Hisato Kawakami, Isamu Okamoto
Sep 29, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Cristina Pérez-RamírezMiguel Ángel Calleja-Hernández
Jul 16, 2010·Journal of Cellular and Molecular Medicine·Ian M BuchananKevin Camphausen
Oct 10, 2013·The Journal of Pathology·Hartmut KoeppenRobert L Yauch
Aug 14, 2010·The Biochemical Journal·Rajkumar GanesanDaniel Kirchhofer
Jun 7, 2015·Cancer Letters·Luigi MaranoAlberto Patriti
Jul 25, 2006·Arthritis Research & Therapy·Serge D SteinfeldOlivier Pradier
Dec 20, 2014·Immunotherapy·Tom WaddellDavid Cunningham
Mar 25, 2017·Experimental & Molecular Medicine·Ki-Hyun Kim, Hyori Kim
Sep 14, 2017·International Journal of Molecular Sciences·Hyunkyu ParkDo-Hyun Nam
Jan 25, 2012·Nature Reviews. Cancer·Ermanno GherardiGeorge Vande Woude
Mar 26, 2016·Oncotarget·Yanni ZhangMingqiang Zhang
Apr 5, 2017·Nature Reviews. Clinical Oncology·Conor A BradleyUNKNOWN MErCuRIC consortium
Aug 24, 2018·Cancers·Oshin MirandaJill M Siegfried
Feb 9, 2020·Oncogene·Jonas P KochMichaela Medová

❮ Previous
Next ❯

Related Concepts

Related Feeds