Anti-Human Met(Onartuzumab) (CAT#: TAB-190-F(E))

Recombinant monoclonal antibody Fragment Fab to Met. Onartuzumab is a humanized monoclonal antibody designed for the treatment of cancer.


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Figure 1 Structural basis for antagonism of MET signaling by onartuzumab.

Figure 1 Structural basis for antagonism of MET signaling by onartuzumab.

(A) Schematic of MET and HGF domain architecture. Functional domains are indicated: Sema domain; PSI domain; Ig-like fold shared by plexins and transcriptional factors (IPT) domain; juxtamembrane (JM) domain; N-terminal (N) domain; kringle (K) domain; serine protease-like (SP-like) domain. The disulfide between the HGF α-and β-chains is shown as a yellow line. Colors used for individual domains in A match those used in D. (B) Competition-binding assays with MET ECD-Fc (encoding MET residues 25-929, which encode the MET Sema domain, the PSI domain, and all four IPT domains) immobilized on plates indicates that onartuzumab blocks HGF-α and NK1, but not HGF-β, binding to MET. (C) Analytical size-exclusion chromatography analysis of onartuzumab, MET Sema-PSI, and HGF-β mixed at 1:2:4 ratio. The three peaks in the chromatogram were visualized by SDS/ PAGE and correspond to the onartuzumab/MET Sema-PSI/HGF-β ternary complex, onartuzumab Fab/HGF-β binary complex, and excess HGF-β. (D) Cartoon representation of the 2.8-Å crystal structure of the onartuzumab Fab/MET Sema-PSI/HGF-β ternary complex (PDB ID code 4K3J) showing the Fab heavy chains (deep purple), Fab light chains (pink), MET Sema (light green) and PSI (deep green) domains, and HGF-β (cyan). The Sema β-propeller is viewed from the "bottom" face and the blades are numbered. (E) Openbook view of the interface between onartuzumab Fab (Left) and human MET Sema-PSI (Right). Residues in the interface were colored according to their percentage of reduction in accessible surface area upon complex formation (15-44%, yellow; 45-74%, orange;>75%, red). Interface analysis was performed using the protein interfaces, surfaces and assemblies (PISA) server (43).

Merchant, M., Ma, X., Maun, H. R., Zheng, Z., Peng, J., Romero, M., ... & Santell, L. (2013). Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent. Proceedings of the National Academy of Sciences, 110(32), E2987-E2996.

Figure 2 Onartuzumab effectively decreases p-MET and total MET in KP4 tumors.

Figure 2 Onartuzumab effectively decreases p-MET and total MET in KP4 tumors.

Immunoprecipitation-immunoblot analysis of p-MET (IP MET and IB p-Try) and total MET (IP and IB MET) in KP4 tumors collected at indicated time points following a single intraperitoneal dose of onartuzumab at 15 mg/kg. N 1⁄4 4/time; pMET 1⁄4 p-MET; tMET 1⁄4 total MET.

Xiang, H., Reyes, A. E., Bender, B. C., Merchant, M., Jumbe, N. L., Romero, M., ... & Peterson, A. (2013). Onartuzumab (MetMAb): using nonclinical pharmacokinetic and concentration-effect data to support clinical development. Clinical Cancer Research, clincanres-0260.

Figure 3 Group mean ( Æ SE) tumor volume – time and corresponding estimated serum concentration – time pro fi les following an intravenous bolus dose of onartuzumab with different dosing regimens in KP4 xenograft mice.

Figure 3 Group mean ( Æ SE) tumor volume – time and corresponding estimated serum concentration – time pro fi les following an intravenous bolus dose of onartuzumab with different dosing regimens in KP4 xenograft mice.

A, tumor volume – time pro fi le and estimated serum concentration using pharmacokinetic parameters obtained from pharmacokinetic study in nontumor-bearing mice following a total intravenous onartuzumab dose at 2.5 mg/kg with Q1W, Q2W, or Q3W dosing. B, tumor volume – time pro fi le and estimated serum concentration – time pro fi le using pharmacokinetic parameters obtained from pharmacokinetic study in nontumor-bearing mice following a total intravenous onartuzumab dose at 7.5 mg/kg with Q1W, Q2W, or Q3W dosing. The vehicle group is the same as in A. C, tumor volume – time pro fi le and estimated serum concentration – time pro fi le using pharmacokinetic parameters obtained from pharmacokinetic study in nontumor-bearing mice following a total intravenous onartuzumab dose at 30 mg/kg with Q1W, Q2W, or Q3W dosing. The vehicle group is the same as in A. The pharmacokinetics parameters used for above simulations are: CL 1⁄4 21.6 mL/d/kg, CL d 1⁄4 190 mL/d/kg, V 1 1⁄4 48.8 mL/kg, and V 2 1⁄4 90.7 mL/kg. Tumor volume was measured on indicated days and is reported as the mean ( Æ SE) for each group. Animals were dosed on day 0 for Q3W dosing; days 0 and 14 for Q2W dosing; and days 0, 7, and 14 for Q1W dosing. n 1⁄4 10 per group. One animal from vehicle control and one from 1.25 mg/kg Q2W groups had tumors that grew too large and the animals were taken off study on day 19. The tumor volume on day 19 was carried forward to day 21 to calculate group mean tumor volume.

Xiang, H., Reyes, A. E., Bender, B. C., Merchant, M., Jumbe, N. L., Romero, M., ... & Peterson, A. (2013). Onartuzumab (MetMAb): using nonclinical pharmacokinetic and concentration-effect data to support clinical development. Clinical Cancer Research, clincanres-0260.

Figure 4 Humanization and affinity maturation of mouse 5D5 to generate onartuzumab, which functionally inhibits HGF/MET signaling.

Figure 4 Humanization and affinity maturation of mouse 5D5 to generate onartuzumab, which functionally inhibits HGF/MET signaling.

Onartuzumab inhibits HGF-dependent MET phosphorylation and downstream activation of GAB1, AKT, ERK1/2, and P70-S6 in a dose-dependent fashion but does not induce any MET signaling in the absence of HGF.

Merchant, M., Ma, X., Maun, H. R., Zheng, Z., Peng, J., Romero, M., ... & Santell, L. (2013). Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent. Proceedings of the National Academy of Sciences, 110(32), E2987-E2996.

Figure 5 Humanization and affinity maturation of mouse 5D5 to generate onartuzumab, which functionally inhibits HGF/MET signaling.

Figure 5 Humanization and affinity maturation of mouse 5D5 to generate onartuzumab, which functionally inhibits HGF/MET signaling.

Onartuzumab inhibits HGF-dependent migration and wound closure in HGF-treated A549 cells with an IC 50 of 20 nM. All plots reflect group mean plus and minus the SEM (n = 3).

Merchant, M., Ma, X., Maun, H. R., Zheng, Z., Peng, J., Romero, M., ... & Santell, L. (2013). Monovalent antibody design and mechanism of action of onartuzumab, a MET antagonist with anti-tumor activity as a therapeutic agent. Proceedings of the National Academy of Sciences, 110(32), E2987-E2996.

Figure 6 Onartuzumab does not trigger MET internalization and prevents HGF-induced internalization.

Figure 6 Onartuzumab does not trigger MET internalization and prevents HGF-induced internalization.

(A) or onartuzumab (B). Cells were kept on ice (blue lines) or shifted to 37°C for 4 hours without (red lines) or with (green lines) exposure to 500 ng/mL human HGF, stained with PE-conjugated anti-murine IgG (3D6) or anti-human IgG (onartuzumab), and analyzed by flow cytometry.

Mai, E., Zheng, Z., Chen, Y., Peng, J., Severin, C., Filvaroff, E., ... & Nijem, I. (2014). Nonclinical evaluation of the serum pharmacodynamic biomarkers HGF and shed MET following dosing with the anti-MET monovalent monoclonal antibody onartuzumab. Molecular cancer therapeutics, 13(2), 540-552.

Figure 7 Onartuzumab does not trigger MET internalization and prevents HGF-induced internalization.

Figure 7 Onartuzumab does not trigger MET internalization and prevents HGF-induced internalization.

HeLa cells were incubated for 4 hours at 37°C with 3D6 without (C) or with 100 μg/mL HGF (D) or onartuzumab without (E) or with HGF (F) and analyzed by immunofluorescence microscopy.

Mai, E., Zheng, Z., Chen, Y., Peng, J., Severin, C., Filvaroff, E., ... & Nijem, I. (2014). Nonclinical evaluation of the serum pharmacodynamic biomarkers HGF and shed MET following dosing with the anti-MET monovalent monoclonal antibody onartuzumab. Molecular cancer therapeutics, 13(2), 540-552.


Specifications

  • Immunogen
  • The details of the immunogen for this antibody are not available.
  • Host Species
  • Mouse
  • Derivation
  • Humanized (from mouse)
  • Type
  • Fab / Fc - G1 - kappa
  • Specificity
  • Tested positive against native human antigen.
  • Species Reactivity
  • Human
  • Applications
  • IP, IF, FuncS, FC, Neut, ELISA, ICC
  • CAS
  • 1133766-06-9
  • Generic Name
  • Onartuzumab
  • UNII
  • MS1J9720WC
  • MW
  • 99.1 kDa
  • Related Disease
  • Solid tumors

Product Property

  • Purity
  • >95.0% as determined by Analysis by RP-HPLC & analysis by SDS-PAGE.
  • Storage
  • Store at -20°C. Avoid multiple freeze/thaw cycles.

Applications

  • Application Notes
  • The MET antibody has been reported in applications of ELISA, IP, PK, WB, Inhib, FC, IF.

Target

  • Alternative Names
  • Onartuzumab;1133766-06-9;MetMAb;PRO143966;RG3638;OA5D5;MET;met proto-oncogene (hepatocyte growth factor receptor);hepatocyte growth factor receptor;HGFR;RCCP2;SF receptor;HGF receptor;oncogene MET;HGF/SF receptor;proto-oncogene c-Met;scatter factor recept

Related Resources

  • Related Diseases

Product Notes

This is a product of Creative Biolabs' Hi-Affi™ recombinant antibody portfolio, which has several benefits including:

• Increased sensitivity
• Confirmed specificity
• High repeatability
• Excellent batch-to-batch consistency
• Sustainable supply
• Animal-free production

See more details about Hi-Affi™ recombinant antibody benefits.

Downloads

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See other products for "MET"

Immunotoxin

CAT Product Name Application Type
AGTO-G049E Anti-MET immunotoxin (Fab)-PE Cytotoxicity assay, Function study

ADCC Enhanced Antibody

CAT Product Name Application Type
PABZ-155 Afuco™ Anti-MET ADCC Recombinant Antibody (Onartuzumab), ADCC Enhanced ELISA, Neut ADCC enhanced antibody
AFC-TAB-H24 Afuco™ Anti-MET ADCC Recombinant Antibody (Emibetuzumab), ADCC Enhanced FuncS, IF, Neut, ELISA, FC, IP ADCC enhanced antibody

Chimeric Antibody

CAT Product Name Application Type
TAB-002MZ Anti-Human MET Recombinant Antibody (MvDN30) IHC, PET imaging Chimeric antibody (mouse/human)
TAB-002MZ-S(P) Anti-Human MET Recombinant Antibody scFv Fragment (MvDN30) IHC, PET imaging Chimeric antibody (mouse/human)
TAB-002MZ-F(E) Anti-Human MET Recombinant Antibody Fab Fragment (MvDN30) IHC, PET imaging Chimeric antibody (mouse/human)
TAB-0880CLV Human Anti-MET Recombinant Antibody (TAB-0880CLV) ELISA, FuncS Chimeric (mouse/human) IgG1
TAB-0880CLV-S(P) Mouse Anti-MET Recombinant Antibody; scFv Fragment (TAB-0880CLV-S(P)) ELISA, FuncS Mouse scFv

Neutralizing Antibody

CAT Product Name Application Type
NEUT-1726CQ Recombinant Rabbit Anti-MET Antibody (CBL1008) Neut IgG

MHC Tetramer for Cancer

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For research use only. Not intended for any clinical use. No products from Creative Biolabs may be resold, modified for resale or used to manufacture commercial products without prior written approval from Creative Biolabs.

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