PMID- 20124448
OWN - NLM
STAT- MEDLINE
DCOM- 20101110
LR  - 20200930
IS  - 1538-8514 (Electronic)
IS  - 1535-7163 (Linking)
VI  - 9
IP  - 2
DP  - 2010 Feb
TI  - Biochemical characterization of AMG 102: a neutralizing, fully human monoclonal 
      antibody to human and nonhuman primate hepatocyte growth factor.
PG  - 400-9
LID - 10.1158/1535-7163.MCT-09-0824 [doi]
AB  - 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-to-mouse 
      amino acid substitutions showed that amino acid residues near the NH(2)-terminus 
      of the beta-chain are critical for AMG 102 binding. Bound AMG 102 protected one 
      trypsin protease cleavage site near the NH(2)-terminus of the beta-chain of human 
      HGF, further substantiating the importance of this region for AMG 102 binding. 
      Currently, AMG 102 is in phase II clinical trials in a variety of solid tumor 
      indications. Mol Cancer Ther; 9(2); 400-9.
FAU - Burgess, Teresa L
AU  - Burgess TL
AD  - Amgen Inc., Thousand Oaks, California 91320-1799, USA. tburgess@amgen.com
FAU - Sun, Jan
AU  - Sun J
FAU - Meyer, Susanne
AU  - Meyer S
FAU - Tsuruda, Trace S
AU  - Tsuruda TS
FAU - Sun, Jilin
AU  - Sun J
FAU - Elliott, Gary
AU  - Elliott G
FAU - Chen, Qing
AU  - Chen Q
FAU - Haniu, Mitsuru
AU  - Haniu M
FAU - Barron, Will F
AU  - Barron WF
FAU - Juan, Todd
AU  - Juan T
FAU - Zhang, Ke
AU  - Zhang K
FAU - Coxon, Angela
AU  - Coxon A
FAU - Kendall, Richard L
AU  - Kendall RL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100202
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Peptide Library)
RN  - 0 (Recombinant Proteins)
RN  - 51WEW898IJ (rilotumumab)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
CIN - Mol Cancer Ther. 2010 May;9(5):1077-9. PMID: 20442310
MH  - Animals
MH  - Antibodies, Monoclonal/*chemistry/pharmacology
MH  - Antibodies, Monoclonal, Humanized
MH  - Epitope Mapping
MH  - Hepatocyte Growth Factor/*chemistry
MH  - Humans
MH  - Immunoblotting
MH  - Inhibitory Concentration 50
MH  - Macaca fascicularis
MH  - Mice
MH  - Peptide Library
MH  - Phosphorylation
MH  - Primates
MH  - Rabbits
MH  - Recombinant Proteins/chemistry
EDAT- 2010/02/04 06:00
MHDA- 2010/11/11 06:00
CRDT- 2010/02/04 06:00
PHST- 2010/02/04 06:00 [entrez]
PHST- 2010/02/04 06:00 [pubmed]
PHST- 2010/11/11 06:00 [medline]
AID - 1535-7163.MCT-09-0824 [pii]
AID - 10.1158/1535-7163.MCT-09-0824 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2010 Feb;9(2):400-9. doi: 10.1158/1535-7163.MCT-09-0824. Epub 
      2010 Feb 2.